Category Archives: Human Genetics

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In the study of rare disorders, four general patterns of inheritance are distinguishable by pedigree analysis: autosomal recessive, autosomal dominant, X-linked recessive, and X-linked dominant.

The affected phenotype of an autosomal recessive disorder is determined by a recessive allele, and the corresponding unaffected phenotype is determined by a dominant allele. For example, the human disease phenylketonuria is inherited in a simple Mendelian manner as a recessive phenotype, with PKU determined by the allele p and the normal condition by P . Therefore, sufferers from this disease are of genotype p /p , and people who do not have the disease are either P /P or P /p . What patterns in a pedigree would reveal such an inheritance? The two key points are that (1) generally the disease appears in the progeny of unaffected parents and (2) the affected progeny include both males and females. When we know that both male and female progeny are affected, we can assume that we are dealing with simple Mendelian inheritance, not sex-linked inheritance. The following typical pedigree illustrates the key point that affected children are born to unaffected parents:

From this pattern, we can immediately deduce simple Mendelian inheritance of the recessive allele responsible for the exceptional phenotype (indicated in black). Furthermore, we can deduce that the parents are both heterozygotes, say A /a ; both must have an a allele because each contributed an a allele to each affected child, and both must have an A allele because they are phenotypically normal. We can identify the genotypes of the children (in the order shown) as A /, a /a , a /a , and A /. Hence, the pedigree can be rewritten as follows:

Note that this pedigree does not support the hypothesis of X-linked recessive inheritance, because, under that hypothesis, an affected daughter must have a heterozygous mother (possible) and a hemizygous father, which is clearly impossible, because he would have expressed the phenotype of the disorder.

Notice another interesting feature of pedigree analysis: even though Mendelian rules are at work, Mendelian ratios are rarely observed in families, because the sample size is too small. In the preceding example, we see a 1:1 phenotypic ratio in the progeny of a monohybrid cross. If the couple were to have, say, 20 children, the ratio would be something like 15 unaffected children and 5 with PKU (a 3:1 ratio); but, in a sample of 4 children, any ratio is possible, and all ratios are commonly found.

The pedigrees of autosomal recessive disorders tend to look rather bare, with few black symbols. A recessive condition shows up in groups of affected siblings, and the people in earlier and later generations tend not to be affected. To understand why this is so, it is important to have some understanding of the genetic structure of populations underlying such rare conditions. By definition, if the condition is rare, most people do not carry the abnormal allele. Furthermore, most of those people who do carry the abnormal allele are heterozygous for it rather than homozygous. The basic reason that heterozygotes are much more common than recessive homozygotes is that, to be a recessive homozygote, both parents must have had the a allele, but, to be a heterozygote, only one parent must carry the a allele.

Geneticists have a quantitative way of connecting the rareness of an allele with the commonness or rarity of heterozygotes and homozygotes in a population. They obtain the relative frequencies of genotypes in a population by assuming that the population is in Hardy-Weinberg equilibrium, to be fully discussed in Chapter 24 . Under this simplifying assumption, if the relative proportions of two alleles A and a in a population are p and q , respectively, then the frequencies of the three possible genotypes are given by p 2 for A /A , 2pq for A /a , and q 2 for a /a . A numerical example illustrates this concept. If we assume that the frequency q of a recessive, disease-causing allele is 1/50, then p is 49/50, the frequency of homozygotes with the disease is q 2 =(1/50)2 =1/250, and the frequency of heterozygotes is 2pq =249/501/50 , or approximately 1/25. Hence, for this example, we see that heterozygotes are 100 times as frequent as disease sufferers, and, as this ratio increases, the rarer the allele becomes. The relation between heterozygotes and homozygotes recessive for a rare allele is shown in the following illustration. Note that the allele frequencies p and q can be used as the gamete frequencies in both sexes.

The formation of an affected person usually depends on the chance union of unrelated heterozygotes. However, inbreeding (mating between relatives) increases the chance that a mating will be between two heterozygotes. An example of a marriage between cousins is shown in . Individuals III-5 and III-6 are first cousins and produce two homozygotes for the rare allele. You can see from that an ancestor who is a heterozygote may produce many descendants who also are heterozygotes. Hence two cousins can carry the same rare recessive allele inherited from a common ancestor. For two unrelated persons to be heterozygous, they would have to inherit the rare allele from both their families. Thus matings between relatives generally run a higher risk of producing abnormal phenotypes caused by homozygosity for recessive alleles than do matings between nonrelatives. For this reason, first-cousin marriages contribute a large proportion of the sufferers of recessive diseases in the population.

Pedigree of a rare recessive phenotype determined by a recessive allele a . Gene symbols are normally not included in pedigree charts, but genotypes are inserted here for reference. Note that individuals II-1 and II-5 marry into the family; they are assumed (more...)

What are some examples of human recessive disorders? PKU has already served as an example of pedigree analysis, but what kind of phenotype is it? PKU is a disease of processing of the amino acid phenylalanine, a component of all proteins in the food that we eat. Phenylalanine is normally converted into tyrosine by the enzyme phenylalanine hydroxylase:

However, if a mutation in the gene encoding this enzyme alters the amino acid sequence in the vicinity of the enzymes active site, the enzyme cannot bind or convert phenylalanine (its substrate). Therefore phenylalanine builds up in the body and is converted instead into phenylpyruvic acid, a compound that interferes with the development of the nervous system, leading to mental retardation.

Babies are now routinely tested for this processing deficiency at birth. If the deficiency is detected, phenylalanine can be withheld by use of a special diet, and the development of the disease can be arrested.

Cystic fibrosis is another disease inherited according to Mendelian rules as a recessive phenotype. The allele that causes cystic fibrosis was isolated in 1989, and the sequence of its DNA was determined. This has led to an understanding of gene function in affected and unaffected persons, giving hope for more effective treatment. Cystic fibrosis is a disease whose most important symptom is the secretion of large amounts of mucus into the lungs, resulting in death from a combination of effects but usually precipitated by upper respiratory infection. The mucus can be dislodged by mechanical chest thumpers, and pulmonary infection can be prevented by antibiotics; so, with treatment, cystic fibrosis patients can live to adulthood. The disorder is caused by a defective protein that transports chloride ions across the cell membrane. The resultant alteration of the salt balance changes the constitution of the lung mucus.

Albinism, which served as a model of allelic determination of contrasting phenotypes in Chapter 1 , also is inherited in the standard autosomal recessive manner. The molecular nature of an albino allele and its inheritance are diagrammed in . This diagram shows a simple autosomal recessive inheritance in a pedigree and shows the molecular nature of the alleles involved. In this example, the recessive allele a is caused by a base pair change that introduces a stop codon into the middle of the gene, resulting in a truncated polypeptide. The mutation, by chance, also introduces a new target site for a restriction enzyme. Hence, a probe for the gene detects two fragments in the case of a and only one in A . (Other types of mutations would produce different effects at the level detected by Southern, Northern, and Western analyses.)

The molecular basis of Mendelian inheritance in a pedigree.

In all the examples heretofore considered, the disorder is caused by an allele for a defective protein. In heterozygotes, the single functional allele provides enough active protein for the cells needs. This situation is called haplosufficiency.

In human pedigrees, an autosomal recessive disorder is revealed by the appearance of the disorder in the male and female progeny of unaffected persons.

Here the normal allele is recessive, and the abnormal allele is dominant. It may seem paradoxical that a rare disorder can be dominant, but remember that dominance and recessiveness are simply properties of how alleles act and are not defined in terms of how common they are in the population. A good example of a rare dominant phenotype with Mendelian inheritance is pseudo-achondroplasia, a type of dwarfism ( ). In regard to this gene, people with normal stature are genotypically d /d , and the dwarf phenotype in principle could be D /d or D /D . However, it is believed that the two doses of the D allele in the D /D genotype produce such a severe effect that this is a lethal genotype. If this is true, all the dwarf individuals are heterozygotes.

The human pseudoachondroplasia phenotype, illustrated by a family of five sisters and two brothers. The phenotype is determined by a dominant allele, which we can call D , that interferes with bone growth during development. Most members of the human population (more...)

In pedigree analysis, the main clues for identifying a dominant disorder with Mendelian inheritance are that the phenotype tends to appear in every generation of the pedigree and that affected fathers and mothers transmit the phenotype to both sons and daughters. Again, the equal representation of both sexes among the affected offspring rules out sex-linked inheritance. The phenotype appears in every generation because generally the abnormal allele carried by a person must have come from a parent in the preceding generation. Abnormal alleles can arise de novo by the process of mutation. This event is relatively rare but must be kept in mind as a possibility. A typical pedigree for a dominant disorder is shown in . Once again, notice that Mendelian ratios are not necessarily observed in families. As with recessive disorders, persons bearing one copy of the rare A allele (A /a ) are much more common than those bearing two copies (A /A ), so most affected people are heterozygotes, and virtually all matings concerning dominant disorders are A /a a /a . Therefore, when the progeny of such matings are totaled, a 1:1 ratio is expected of unaffected (a /a ) to affected (A /a ) persons.

Pedigree of a dominant phenotype determined by a dominant allele A . In this pedigree, all the genotypes have been deduced.

Huntington disease is an example of a disease inherited as a dominant phenotype determined by an allele of a single gene. The phenotype is one of neural degeneration, leading to convulsions and premature death. However, it is a late-onset disease, the symptoms generally not appearing until after the person has begun to have children ( ). Each child of a carrier of the abnormal allele stands a 50 percent chance of inheriting the allele and the associated disease. This tragic pattern has led to a great effort to find ways of identifying people who carry the abnormal allele before they experience the onset of the disease. The application of molecular techniques has resulted in a promising screening procedure.

The age of onset of Huntington disease. The graph shows that people carrying the allele generally do not express the disease until after child-bearing age.

Some other rare dominant conditions are polydactyly (extra digits) and brachydactyly (short digits), shown in , and piebald spotting, shown in .

Some rare dominant phenotypes of the human hand. (a) (right) Polydactyly, a dominant phenotype characterized by extra fingers, toes, or both, determined by an allele P . The numbers in the accompanying pedigree (left) give the number of fingers in the (more...)

Piebald spotting, a rare dominant human phenotype. Although the phenotype is encountered sporadically in all races, the patterns show up best in those with dark skin. (a) The photographs show front and back views of affected persons IV-1, IV-3, III-5, (more...)

Pedigrees of Mendelian autosomal dominant disorders show affected males and females in each generation; they also show that affected men and women transmit the condition to equal proportions of their sons and daughters.

Phenotypes with X-linked recessive inheritance typically show the following patterns in pedigrees:

Many more males than females show the phenotype under study. This is because a female showing the phenotype can result only from a mating in which both the mother and the father bear the allele (for example, XA Xa Xa Y), whereas a male with the phenotype can be produced when only the mother carries the allele. If the recessive allele is very rare, almost all persons showing the phenotype are male.

None of the offspring of an affected male are affected, but all his daughters are carriers, bearing the recessive allele masked in the heterozygous condition. Half of the sons of these carrier daughters are affected ( ). Note that, in common X-linked phenotypes, this pattern might be obscured by inheritance of the recessive allele from a heterozygous mother as well as the father.

None of the sons of an affected male show the phenotype under study, nor will they pass the condition to their offspring. The reason behind this lack of male-to-male transmission is that a son obtains his Y chromosome from his father, so he cannot normally inherit the fathers X chromosome too.

Pedigree showing that X-linked recessive alleles expressed in males are then carried unexpressed by their daughters in the next generation, to be expressed again in their sons. Note that III-3 and III-4 cannot be distinguished phenotypically.

In the pedigree analysis of rare X-linked recessives, a normal female of unknown genotype is assumed to be homo-zygous unless there is evidence to the contrary.

Perhaps the most familiar example of X-linked recessive inheritance is red-green colorblindness. People with this condition are unable to distinguish red from green and see them as the same. The genes for color vision have been characterized at the molecular level. Color vision is based on three different kinds of cone cells in the retina, each sensitive to red, green, or blue wavelengths. The genetic determinants for the red and green cone cells are on the X chromosome. As with any X-linked recessive, there are many more males with the phenotype than females.

Another familiar example is hemophilia, the failure of blood to clot. Many proteins must interact in sequence to make blood clot. The most common type of hemophilia is caused by the absence or malfunction of one of these proteins, called Factor VIII. The most well known cases of hemophilia are found in the pedigree of interrelated royal families in Europe ( ). The original hemophilia allele in the pedigree arose spontaneously (as a mutation) either in the reproductive cells of Queen Victorias parents or of Queen Victoria herself. The son of the last czar of Russia, Alexis, inherited the allele ultimately from Queen Victoria, who was the grandmother of his mother Alexandra. Nowadays, hemophilia can be treated medically, but it was formerly a potentially fatal condition. It is interesting to note that, in the Jewish Talmud, there are rules about exemptions to male circumcision that show clearly that the mode of transmission of the disease through unaffected carrier females was well understood in ancient times. For example, one exemption was for the sons of women whose sisters sons had bled profusely when they were circumcised.

The inheritance of the X-linked recessive condition hemophilia in the royal families of Europe. A recessive allele causing hemophilia (failure of blood clotting) arose in the reproductive cells of Queen Victoria, or one of her parents, through mutation. (more...)

Duchenne muscular dystrophy is a fatal X-linked recessive disease. The phenotype is a wasting and atrophy of muscles. Generally the onset is before the age of 6, with confinement to a wheelchair by 12, and death by 20. The gene for Duchenne muscular dystrophy has now been isolated and shown to encode the muscle protein dystrophin. This discovery holds out hope for a better understanding of the physiology of this condition and, ultimately, a therapy.

A rare X-linked recessive phenotype that is interesting from the point of view of sexual differentiation is a condition called testicular feminization syndrome, which has a frequency of about 1 in 65,000 male births. People afflicted with this syndrome are chromosomally males, having 44 autosomes plus an X and a Y, but they develop as females ( ). They have female external genitalia, a blind vagina, and no uterus. Testes may be present either in the labia or in the abdomen. Although many such persons marry, they are sterile. The condition is not reversed by treatment with the male hormone androgen, so it is sometimes called androgen insensitivity syndrome. The reason for the insensitivity is that the androgen receptor malfunctions, so the male hormone can have no effect on the target organs that contribute to maleness. In humans, femaleness results when the male-determining system is not functional.

Four siblings with testicular feminization syndrome (congenital insensitivity to androgens). All four subjects in this photograph have 44 autosomes plus an X and a Y chromosome, but they have inherited the recessive X-linked allele conferring insensitivity to (more...)

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Human genetics - An Introduction to Genetic Analysis ...

Some cells are visible to the unaided eye

The smallest objects that the unaided human eye can see are about 0.1 mm long. That means that under the right conditions, you might be able to see an ameoba proteus, a human egg, and a paramecium without using magnification. A magnifying glass can help you to see them more clearly, but they will still look tiny.

Smaller cells are easily visible under a light microscope. It's even possible to make out structures within the cell, such as the nucleus, mitochondria and chloroplasts. Light microscopes use a system of lenses to magnify an image. The power of a light microscope is limited by the wavelength of visible light, which is about 500 nm. The most powerful light microscopes can resolve bacteria but not viruses.

To see anything smaller than 500 nm, you will need an electron microscope. Electron microscopes shoot a high-voltage beam of electrons onto or through an object, which deflects and absorbs some of the electrons. Resolution is still limited by the wavelength of the electron beam, but this wavelength is much smaller than that of visible light. The most powerful electron microscopes can resolve molecules and even individual atoms.

The label on the nucleotide is not quite accurate. Adenine refers to a portion of the molecule, the nitrogenous base. It would be more accurate to label the nucleotide deoxyadenosine monophosphate, as it includes the sugar deoxyribose and a phosphate group in addition to the nitrogenous base. However, the more familiar "adenine" label makes it easier for people to recognize it as one of the building blocks of DNA.

No, this isn't a mistake. First, there's less DNA in a sperm cell than there is in a non-reproductive cell such as a skin cell. Second, the DNA in a sperm cell is super-condensed and compacted into a highly dense form. Third, the head of a sperm cell is almost all nucleus. Most of the cytoplasm has been squeezed out in order to make the sperm an efficient torpedo-like swimming machine.

The X chromosome is shown here in a condensed state, as it would appear in a cell that's going through mitosis. It has also been duplicated, so there are actually two identical copies stuck together at their middles. A human sperm cell contains just one copy each of 23 chromosomes.

A chromosome is made up of genetic material (one long piece of DNA) wrapped around structural support proteins (histones). Histones organize the DNA and keep it from getting tangled, much like thread wrapped around a spool. But they also add a lot of bulk. In a sperm cell, a specialized set of tiny support proteins (protamines) pack the DNA down to about one-sixth the volume of a mitotic chromosome.

The size of the carbon atom is based on its van der Waals radius.

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Cell Size and Scale - Learn Genetics

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Track 10:Comparative Genomics

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RelatedConferences: InternationalConferenceonPlantPhysiologyJune 09-11, 2016 Dallas, USA ;GlobalSummit onPlant ScienceNovember 28-30, 2016 Baltimore, USA; 5th InternationalConferenceonAgricultureand HorticultureJune 27-29, 2016 Cape Town, South Africa ; 6th InternationalConferenceonGenomicsand PharmacogenomicsSeptember 22-24, 2016 Berlin, Germany; InternationalConferenceonGreen Energy& ExpoNovember 28-30, 2016 Baltimore, USA;PlantGenomes andBiotechnology: from genes to networks Dec ember 02-05, 2015 Berlin, Germany; Plant Genome Evolution 2015 September, 6 - 8 2015 Amsterdam, The Netherlands; The 3rdPlant GenomicsCongressSeptember 14-15,2015 Missouri, USA; ProkaGENOMICS EuropeanConferenceonProkaryoticandFungalGenomics29 September-2 October 2015 Gttingen, Germany; InternationalMeetingonBioinformaticsand OMICs October 27- 30,2015 Varadero, Cuba; The 2ndPlant GenomicsCongress: September 14-15, 2015 MO, USA; GETGlobal ConferenceSeptember17-19, 2015 Vienna, Austria

Track 12:Personal Genomics

Individualgenomicsis the branch of genomics worried with thesequencingand examination of the genome of a person. Thegenotypingstage utilizes diverse strategies, includingsingle-nucleotide polymorphism(SNP) examination chips or incomplete or fullgenome sequencing.

RelatedConferences: 4th InternationalConferenceonIntegrativeBiology, July 18-20, 2016, Berlin, Germany; 2nd InternationalConferenceonTranscriptomicsAugust 18-20, 2016 Portland, Oregon USA; InternationalConferenceonNextGenerationSequencingJuly 21-22, 2016 Berlin, Germany;WorldCongress onHumanGeneticsOctober 31- November 02, 2016 Valencia, Spain; 18th InternationalConference onHuman Genetics, February 25 - 26, 2016, London, United Kingdom;Visualizing biological data, 911 March 2016, Heidelberg, Germany; 1st Annual InternationalCongressofGenetics, April 25-28, Dalian, China;ChromatinandEpigenetics, March 20-24, 2016, British Columbia,Canada;GameofEpigenetics, April 24-28, 2016 in Dubrovnik

Track 13:Microbial Genomics

MicrobialGenomicsappliesrecombinantDNA,DNAsequencingroutines,andbioinformaticsto succession, gather, and dissect the capacity and structure of genomes in organisms. Amid the previous 10 years, genomics-based methodologies have profoundly affected the field ofmicrobiologyand our comprehension of microbial species. In view of their bigger genome sizes,genome sequencingendeavors on growths and unicellular eukaryotes were slower to begin than ventures concentrated on prokaryotes.

RelatedConferences: InternationalConferenceonMolecular BiologyOctober 13-15, 2016 Dubai, UAE; 4th InternationalConferenceonIntegrativeBiologyJuly 18-20, 2016 Berlin, Germany; InternationalConference onMicrobial Physiology and Genomics October 20-22, 2016 Rome, Italy; 4th InternationalConference onClinicalMicrobiologyandMicrobialGenomics October 05-07, 2015 Philadelphia, USA; 2ndWorld CongressandExpoonAppliedMicrobiologyOctober 31-November 02, 2016 Istanbul, Turkey; 18th InternationalConferenceonClinicalMicrobiologyandMicrobialGenomics, June 9 - 10, 2016, San Francisco, USA; 18th InternationalConferenceonMicrobialGenomeResources, February 11 - 12, 2016, Kuala Lumpur, Malaysia; 18th InternationalConferenceonMicrobialGenomeResourcesand Clinical Microbiology, January 12 - 13, 2016, Zurich, Switzerland; 18th InternationalConference onMolecular Geneticsand Microbiology, February 25 - 26, 2016, London, United Kingdom

Track 14:Future trends in Genomics

Genomics researchholds the way to meeting a considerable lot of the difficulties of the coming years. Right now, the greatest test is in information investigation. We can produce a lot of information modestly, yet that overpowers our ability to comprehend it. The significant test of theGenomeResearch is we have to imbuegenomic datainto restorative practice, which is truly hard.

RelatedConferences: InternationalConferenceonClinical and Molecular Genetics, November 28-30, 2016 Chicago, USA; 2nd InternationalConferenceonTranscriptomicsAugust 18-20, 2016 Portland, Oregon USA;International ConferenceonNextGenerationSequencingJuly 21-22, 2016 Berlin, Germany; The FourteenthAsia PacificBioinformaticsConference, 11th-13 January 2016, San Francisco, USA;WorldCongress onHumanGeneticsOctober 31- November 02, 2016 Valencia, Spain; 18th InternationalConference onGeneticsand Genomics, June 9 - 10, 2016, San Francisco, USA; NGS 16Genome Annotation, April 4 6, 2016, Barcelona, Spain; Maintenance of Genome Stability 2016, March 7-10, 2016, Panama, Central America;Epigenomics: new marks, new horizons, December 2015, 2 December 2015, UK;Human GenomeMeeting, 28 February 2 March 2016, Houston, USA

Track15:GenomicMedicine GenomicMedicineas "a developing restorative train that includes utilizinggenomicdataaround a person as a major aspect of their clinical consideration (e.g., for demonstrative or remedial choice making) and the wellbeing results and strategy ramifications of that clinical use." Already,genomic medicationis having an effect in the fields ofoncology,pharmacology, uncommon and undiscovered maladies, and irresistible illness.

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Track 16:Genomics Market

Genomicsis the study of thegenetic materialor genomes of an organism. Analysts forecast theGlobal Genomicsmarketwill grow at a CAGR of 11.21% over the period 2013-2018. According to the report, the most important driver of the market is an increase in the demand for consumables. The growing adoption ofgenetictestingfor various applications, especially in regions such as the APAC, and an increase ingenetictestingvolumes in North America and Western Europe is increasing the demand for consumables.

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Originally posted here:
Worlds Leading Genomics Conference | Global Meetings ...

Genetics is the scientific study of inherited variation. Human genetics, then, is the scientific study of inherited human variation.

Why study human genetics? One reason is simply an interest in better understanding ourselves. As a branch of genetics, human genetics concerns itself with what most of us consider to be the most interesting species on earth: Homo sapiens. But our interest in human genetics does not stop at the boundaries of the species, for what we learn about human genetic variation and its sources and transmission inevitably contributes to our understanding of genetics in general, just as the study of variation in other species informs our understanding of our own.

A second reason for studying human genetics is its practical value for human welfare. In this sense, human genetics is more an applied science than a fundamental science. One benefit of studying human genetic variation is the discovery and description of the genetic contribution to many human diseases. This is an increasingly powerful motivation in light of our growing understanding of the contribution that genes make to the development of diseases such as cancer, heart disease, and diabetes. In fact, society has been willing in the past and continues to be willing to pay significant amounts of money for research in this area, primarily because of its perception that such study has enormous potential to improve human health. This perception, and its realization in the discoveries of the past 20 years, have led to a marked increase in the number of people and organizations involved in human genetics.

This second reason for studying human genetics is related to the first. The desire to develop medical practices that can alleviate the suffering associated with human disease has provided strong support to basic research. Many basic biological phenomena have been discovered and described during the course of investigations into particular disease conditions. A classic example is the knowledge about human sex chromosomes that was gained through the study of patients with sex chromosome abnormalities. A more current example is our rapidly increasing understanding of the mechanisms that regulate cell growth and reproduction, understanding that we have gained primarily through a study of genes that, when mutated, increase the risk of cancer.

Likewise, the results of basic research inform and stimulate research into human disease. For example, the development of recombinant DNA techniques () rapidly transformed the study of human genetics, ultimately allowing scientists to study the detailed structure and functions of individual human genes, as well as to manipulate these genes in a variety of previously unimaginable ways.

Recombinant techniques have transformed the study of human genetics.

A third reason for studying human genetics is that it gives us a powerful tool for understanding and describing human evolution. At one time, data from physical anthropology (including information about skin color, body build, and facial traits) were the only source of information available to scholars interested in tracing human evolutionary history. Today, however, researchers have a wealth of genetic data, including molecular data, to call upon in their work.

Two research approaches were historically important in helping investigators understand the biological basis of heredity. The first of these approaches, transmission genetics, involved crossing organisms and studying the offsprings' traits to develop hypotheses about the mechanisms of inheritance. This work demonstrated that in some organisms at least, heredity seems to follow a few definite and rather simple rules.

The second approach involved using cytologic techniques to study the machinery and processes of cellular reproduction. This approach laid a solid foundation for the more conceptual understanding of inheritance that developed as a result of transmission genetics. By the early 1900s, cytologists had demonstrated that heredity is the consequence of the genetic continuity of cells by cell division, had identified the gametes as the vehicles that transmit genetic information from one generation to another, and had collected strong evidence for the central role of the nucleus and the chromosomes in heredity.

As important as they were, the techniques of transmission genetics and cytology were not enough to help scientists understand human genetic variation at the level of detail that is now possible. The central advantage that today's molecular techniques offer is that they allow researchers to study DNA directly. Before the development of these techniques, scientists studying human genetic variation were forced to make inferences about molecular differences from the phenotypes produced by mutant genes. Furthermore, because the genes associated with most single-gene disorders are relatively rare, they could be studied in only a small number of families. Many of the traits associated with these genes also are recessive and so could not be detected in people with heterozygous genotypes. Unlike researchers working with other species, human geneticists are restricted by ethical considerations from performing experimental, "at-will" crosses on human subjects. In addition, human generations are on the order of 20 to 40 years, much too slow to be useful in classic breeding experiments. All of these limitations made identifying and studying genes in humans both tedious and slow.

In the last 50 years, however, beginning with the discovery of the structure of DNA and accelerating significantly with the development of recombinant DNA techniques in the mid-1970s, a growing battery of molecular techniques has made direct study of human DNA a reality. Key among these techniques are restriction analysis and molecular recombination, which allow researchers to cut and rejoin DNA molecules in highly specific and predictable ways; amplification techniques, such as the polymerase chain reaction (PCR), which make it possible to make unlimited copies of any fragment of DNA; hybridization techniques, such as fluorescence in situ hybridization, which allow scientists to compare DNA samples from different sources and to locate specific base sequences within samples; and the automated sequencing techniques that today are allowing workers to sequence the human genome at an unprecedented rate.

On the immediate horizon are even more powerful techniques, techniques that scientists expect will have a formidable impact on the future of both research and clinical genetics. One such technique, DNA chip technology (also called DNA microarray technology), is a revolutionary new tool designed to identify mutations in genes or survey expression of tens of thousands of genes in one experiment.

In one application of this technology, the chip is designed to detect mutations in a particular gene. The DNA microchip consists of a small glass plate encased in plastic. It is manufactured using a process similar to the process used to make computer microchips. On its surface, it contains synthetic single-stranded DNA sequences identical to that of the normal gene and all possible mutations of that gene. To determine whether an individual possesses a mutation in the gene, a scientist first obtains a sample of DNA from the person's blood, as well as a sample of DNA that does not contain a mutation in that gene. After denaturing, or separating, the DNA samples into single strands and cutting them into smaller, more manageable fragments, the scientist labels the fragments with fluorescent dyes: the person's DNA with red dye and the normal DNA with green dye. Both sets of labeled DNA are allowed to hybridize, or bind, to the synthetic DNA on the chip. If the person does not have a mutation in the gene, both DNA samples will hybridize equivalently to the chip and the chip will appear uniformly yellow. However, if the person does possess a mutation, the mutant sequence on the chip will hybridize to the patient's sample, but not to the normal DNA, causing it (the chip) to appear red in that area. The scientist can then examine this area more closely to confirm that a mutation is present.

DNA microarray technology is also allowing scientists to investigate the activity in different cell types of thousands of genes at the same time, an advance that will help researchers determine the complex functional relationships that exist between individual genes. This type of analysis involves placing small snippets of DNA from hundreds or thousands of genes on a single microscope slide, then allowing fluorescently labeled mRNA molecules from a particular cell type to hybridize to them. By measuring the fluorescence of each spot on the slide, scientists can determine how active various genes are in that cell type. Strong fluorescence indicates that many mRNA molecules hybridized to the gene and, therefore, that the gene is very active in that cell type. Conversely, no fluorescence indicates that none of the cell's mRNA molecules hybridized to the gene and that the gene is inactive in that cell type.

Although these technologies are still relatively new and are being used primarily for research, scientists expect that one day they will have significant clinical applications. For example, DNA chip technology has the potential to significantly reduce the time and expense involved in genetic testing. This technology or others like it may one day help make it possible to define an individual's risk of developing many types of hereditary cancer as well as other common disorders, such as heart disease and diabetes. Likewise, scientists may one day be able to classify human cancers based on the patterns of gene activity in the tumor cells and then be able to design treatment strategies that are targeted directly to each specific type of cancer.

Homo sapiens is a relatively young species and has not had as much time to accumulate genetic variation as have the vast majority of species on earth, most of which predate humans by enormous expanses of time. Nonetheless, there is considerable genetic variation in our species. The human genome comprises about 3 109 base pairs of DNA, and the extent of human genetic variation is such that no two humans, save identical twins, ever have been or will be genetically identical. Between any two humans, the amount of genetic variationbiochemical individualityis about .1 percent. This means that about one base pair out of every 1,000 will be different between any two individuals. Any two (diploid) people have about 6 106 base pairs that are different, an important reason for the development of automated procedures to analyze genetic variation.

The most common polymorphisms (or genetic differences) in the human genome are single base-pair differences. Scientists call these differences SNPs, for single-nucleotide polymorphisms. When two different haploid genomes are compared, SNPs occur, on average, about every 1,000 bases. Other types of polymorphismsfor example, differences in copy number, insertions, deletions, duplications, and rearrangementsalso occur, but much less frequently.

Notwithstanding the genetic differences between individuals, all humans have a great deal of their genetic information in common. These similarities help define us as a species. Furthermore, genetic variation around the world is distributed in a rather continuous manner; there are no sharp, discontinuous boundaries between human population groups. In fact, research results consistently demonstrate that about 85 percent of all human genetic variation exists within human populations, whereas about only 15 percent of variation exists between populations (). That is, research reveals that Homo sapiens is one continuously variable, interbreeding species. Ongoing investigation of human genetic variation has even led biologists and physical anthropologists to rethink traditional notions of human racial groups. The amount of genetic variation between these traditional classifications actually falls below the level that taxonomists use to designate subspecies, the taxonomic category for other species that corresponds to the designation of race in Homo sapiens. This finding has caused some biologists to call the validity of race as a biological construct into serious question.

Most variation occurs within populations.

Analysis of human genetic variation also confirms that humans share much of their genetic information with the rest of the natural worldan indication of the relatedness of all life by descent with modification from common ancestors. The highly conserved nature of many genetic regions across considerable evolutionary distance is especially obvious in genes related to development. For example, mutations in the patched gene produce developmental abnormalities in Drosophila, and mutations in the patched homolog in humans produce analogous structural deformities in the developing human embryo.

Geneticists have used the reality of evolutionary conservation to detect genetic variations associated with some cancers. For example, mutations in the genes responsible for repair of DNA mismatches that arise during DNA replication are associated with one form of colon cancer. These mismatched repair genes are conserved in evolutionary history all the way back to the bacterium Escherichia coli, where the genes are designated Mutl and Muts. Geneticists suspected that this form of colon cancer was associated with a failure of mismatch repair, and they used the known sequences from the E. coli genes to probe the human genome for homologous sequences. This work led ultimately to the identification of a gene that is associated with increased risk for colon cancer.

Almost all human genetic variation is relatively insignificant biologically; that is, it has no adaptive significance. Some variation (for example, a neutral mutation) alters the amino acid sequence of the resulting protein but produces no detectable change in its function. Other variation (for example, a silent mutation) does not even change the amino acid sequence. Furthermore, only a small percentage of the DNA sequences in the human genome are coding sequences (sequences that are ultimately translated into protein) or regulatory sequences (sequences that can influence the level, timing, and tissue specificity of gene expression). Differences that occur elsewhere in the DNAin the vast majority of the DNA that has no known functionhave no impact.

Some genetic variation, however, can be positive, providing an advantage in changing environments. The classic example from the high school biology curriculum is the mutation for sickle hemoglobin, which in the heterozygous state provides a selective advantage in areas where malaria is endemic.

More recent examples include mutations in the CCR5 gene that appear to provide protection against AIDS. The CCR5 gene encodes a protein on the surface of human immune cells. HIV, the virus that causes AIDS, infects immune cells by binding to this protein and another protein on the surface of those cells. Mutations in the CCR5 gene that alter its level of expression or the structure of the resulting protein can decrease HIV infection. Early research on one genetic variant indicates that it may have risen to high frequency in Northern Europe about 700 years ago, at about the time of the European epidemic of bubonic plague. This finding has led some scientists to hypothesize that the CCR5 mutation may have provided protection against infection by Yersinia pestis, the bacterium that causes plague. The fact that HIV and Y. pestis both infect macrophages supports the argument for selective advantage of this genetic variant.

The sickle cell and AIDS/plague stories remind us that the biological significance of genetic variation depends on the environment in which genes are expressed. It also reminds us that differential selection and evolution would not proceed in the absence of genetic variation within a species.

Some genetic variation, of course, is associated with disease, as classic single-gene disorders such as sickle cell disease, cystic fibrosis, and Duchenne muscular dystrophy remind us. Increasingly, research also is uncovering genetic variations associated with the more common diseases that are among the major causes of sickness and death in developed countriesdiseases such as heart disease, cancer, diabetes, and psychiatric disorders such as schizophrenia and bipolar disease (manic-depression). Whereas disorders such as cystic fibrosis or Huntington disease result from the effects of mutation in a single gene and are evident in virtually all environments, the more common diseases result from the interaction of multiple genes and environmental variables. Such diseases therefore are termed polygenic and multifactorial. In fact, the vast majority of human traits, diseases or otherwise, are multifactorial.

The genetic distinctions between relatively rare single-gene disorders and the more common multifactorial diseases are significant. Genetic variations that underlie single-gene disorders generally are relatively recent, and they often have a major, detrimental impact, disrupting homeostasis in significant ways. Such disorders also generally exact their toll early in life, often before the end of childhood. In contrast, the genetic variations that underlie common, multifactorial diseases generally are of older origin and have a smaller, more gradual effect on homeostasis. They also generally have their onset in adulthood. The last two characteristics make the ability to detect genetic variations that predispose/increase risk of common diseases especially valuable because people have time to modify their behavior in ways that can reduce the likelihood that the disease will develop, even against a background of genetic predisposition.

As noted earlier, one of the benefits of understanding human genetic variation is its practical value for understanding and promoting health and for understanding and combating disease. We probably cannot overestimate the importance of this benefit. First, as shows, virtually every human disease has a genetic component. In some diseases, such as Huntington disease, Tay-Sachs disease, and cystic fibrosis, this component is very large. In other diseases, such as cancer, diabetes, and heart disease, the genetic component is more modest. In fact, we do not typically think of these diseases as "genetic diseases," because we inherit not the certainty of developing a disease, but only a predisposition to developing it.

Virtually all human diseases, except perhaps trauma, have a genetic component.

In still other diseases, the genetic component is very small. The crucial point, however, is that it is there. Even infectious diseases, diseases that we have traditionally placed in a completely different category than genetic disorders, have a real, albeit small, genetic component. For example, as the CCR5 example described earlier illustrates, even AIDS is influenced by a person's genotype. In fact, some people appear to have genetic resistance to HIV infection as a result of carrying a variant of the CCR5 gene.

Second, each of us is at some genetic risk, and therefore can benefit, at least theoretically, from the progress scientists are making in understanding and learning how to respond to these risks. Scientists estimate that each of us carries between 5 and 50 mutations that carry some risk for disease or disability. Some of us may not experience negative consequences from the mutations we carry, either because we do not live long enough for it to happen or because we may not be exposed to the relevant environmental triggers. The reality, however, is that the potential for negative consequences from our genes exists for each of us.

How is modern genetics helping us address the challenge of human disease? As shows, modern genetic analysis of a human disease begins with mapping and cloning the associated gene or genes. Some of the earliest disease genes to be mapped and cloned were the genes associated with Duchenne muscular dystrophy, retinoblastoma, and cystic fibrosis. More recently, scientists have announced the cloning of genes for breast cancer, diabetes, and Parkinson disease.

Mapping and cloning a gene can lead to strategies that reduce the risk of disease (preventive medicine); guidelines for prescribing drugs based on a person's genotype (pharmacogenomics); procedures that alter the affected gene (gene therapy); or drugs (more...)

As also shows, mapping and cloning a disease-related gene opens the way for the development of a variety of new health care strategies. At one end of the spectrum are genetic tests intended to identify people at increased risk for the disease and recognize genotypic differences that have implications for effective treatment. At the other end are new drug and gene therapies that specifically target the biochemical mechanisms that underlie the disease symptoms or even replace, manipulate, or supplement nonfunctional genes with functional ones. Indeed, as suggests, we are entering the era of molecular medicine.

Genetic testing is not a new health care strategy. Newborn screening for diseases like PKU has been going on for 30 years in many states. Nevertheless, the remarkable progress scientists are making in mapping and cloning human disease genes brings with it the prospect for the development of more genetic tests in the future. The availability of such tests can have a significant impact on the way the public perceives a particular disease and can also change the pattern of care that people in affected families might seek and receive. For example, the identification of the BRCA1 and BRCA2 genes and the demonstration that particular variants of these genes are associated with an increased risk of breast and ovarian cancer have paved the way for the development of guidelines and protocols for testing individuals with a family history of these diseases. BRCA1, located on the long arm of chromosome 17, was the first to be isolated, and variants of this gene account for about 50 percent of all inherited breast cancer, or about 5 percent of all breast cancer. Variants of BRCA2, located on the long arm of chromosome 13, appear to account for about 30 to 40 percent of all inherited breast cancer. Variants of these genes also increase slightly the risk for men of developing breast, prostate, or possibly other cancers.

Scientists estimate that hundreds of thousands of women in the United States have 1 of hundreds of significant mutations already detected in the BRCA1 gene. For a woman with a family history of breast cancer, the knowledge that she carries one of the variants of BRCA1 or BRCA2 associated with increased risk can be important information. If she does carry one of these variants, she and her physician can consider several changes in her health care, such as increasing the frequency of physical examinations; introducing mammography at an earlier age; and even having prophylactic mastectomy. In the future, drugs may also be available that decrease the risk of developing breast cancer.

The ability to test for the presence in individuals of particular gene variants is also changing the way drugs are prescribed and developed. A rapidly growing field known as pharmacogenomics focuses on crucial genetic differences that cause drugs to work well in some people and less well, or with dangerous adverse reactions, in others. For example, researchers investigating Alzheimer disease have found that the way patients respond to drug treatment can depend on which of three genetic variants of the ApoE (Apolipoprotein E) gene a person carries. Likewise, some of the variability in children's responses to therapeutic doses of albuterol, a drug used to treat asthma, was recently linked to genotypic differences in the beta-2-adrenergic receptor. Because beta-2-adrenergic receptor agonists (of which albuterol is one) are the most widely used agents in the treatment of asthma, these results may have profound implications for understanding the genetic factors that determine an individual's response to asthma therapy.

Experts predict that increasingly in the future, physicians will use genetic tests to match drugs to an individual patient's body chemistry, so that the safest and most effective drugs and dosages can be prescribed. After identifying the genotypes that determine individual responses to particular drugs, pharmaceutical companies also likely will set out to develop new, highly specific drugs and revive older ones whose effects seemed in the past too unpredictable to be of clinical value.

Knowledge of the molecular structure of disease-related genes also is changing the way researchers approach developing new drugs. A striking example followed the discovery in 1989 of the gene associated with cystic fibrosis (CF). Researchers began to study the function of the normal and defective proteins involved in order to understand the biochemical consequences of the gene's variant forms and to develop new treatment strategies based on that knowledge. The normal protein, called CFTR for cystic fibrosis transmembrane conductance regulator, is embedded in the membranes of several cell types in the body, where it serves as a channel, transporting chloride ions out of the cells. In CF patients, depending on the particular mutation the individual carries, the CFTR protein may be reduced or missing from the cell membrane, or may be present but not function properly. In some mutations, synthesis of CFTR protein is interrupted, and the cells produce no CFTR molecules at all.

Although all of the mutations associated with CF impair chloride transport, the consequences for patients with different mutations vary. For example, patients with mutations causing absent or markedly reduced CFTR protein may have more severe disease than patients with mutations in which CFTR is present but has altered function. The different mutations also suggest different treatment strategies. For example, the most common CF-related mutation (called delta F508) leads to the production of protein molecules (called delta F508 CFTR) that are misprocessed and are degraded prematurely before they reach the cell membrane. This finding suggests that drug treatments that would enhance transport of the defective delta F508 protein to the cell membrane or prevent its degradation could yield important benefits for patients with delta F508 CFTR.

Finally, the identification, cloning, and sequencing of a disease-related gene can open the door to the development of strategies for treating the disease using the instructions encoded in the gene itself. Collectively referred to as gene therapy, these strategies typically involve adding a copy of the normal variant of a disease-related gene to a patient's cells. The most familiar examples of this type of gene therapy are cases in which researchers use a vector to introduce the normal variant of a disease-related gene into a patient's cells and then return those cells to the patient's body to provide the function that was missing. This strategy was first used in the early 1990s to introduce the normal allele of the adenosine deaminase (ADA) gene into the body of a little girl who had been born with ADA deficiency. In this disease, an abnormal variant of the ADA gene fails to make adenosine deaminase, a protein that is required for the correct functioning of T-lymphocytes.

Although researchers are continuing to refine this general approach to gene therapy, they also are developing new approaches. For example, scientists hope that one very new strategy, called chimeraplasty, may one day be used to actually correct genetic defects that involve only a single base change. Chimeraplasty uses specially synthesized molecules that base pair with a patient's DNA and stimulate the cell's normal DNA repair mechanisms to remove the incorrect base and substitute the correct one. At this point, chimeraplasty is still in early development and the first clinical trials are about to get underway.

Yet another approach to gene therapy involves providing new or altered functions to a cell through the introduction of new genetic information. For example, recent experiments have demonstrated that it is possible, under carefully controlled experimental conditions, to introduce genetic information into cancer cells that will alter their metabolism so that they commit suicide when exposed to a normally innocuous environmental trigger. Researchers are also using similar experiments to investigate the feasibility of introducing genetic changes into cells that will make them immune to infection by HIV. Although this research is currently being done only in nonhuman primates, it may eventually benefit patients infected with HIV.

As indicates, the Human Genome Project (HGP) has significantly accelerated the pace of both the discovery of human genes and the development of new health care strategies based on a knowledge of a gene's structure and function. The new knowledge and technologies emerging from HGP-related research also are reducing the cost of finding human genes. For example, the search for the gene associated with cystic fibrosis, which ended in 1989, before the inception of the HGP, required more than eight years and $50 million. In contrast, finding a gene associated with a Mendelian disorder now can be accomplished in less than a year at a cost of approximately $100,000.

The last few years of research into human genetic variation also have seen a gradual transition from a primary focus on genes associated with single-gene disorders, which are relatively rare in the human population, to an increasing focus on genes associated with multifactorial diseases. Because these diseases are not rare, we can expect that this work will affect many more people. Understanding the genetic and environmental bases for these multifactorial diseases also will lead to increased testing and the development of new interventions that likely will have an enormous effect on the practice of medicine in the next century.

What are the implications of using our growing knowledge of human genetic variation to improve personal and public health? As noted earlier, the rapid pace of the discovery of genetic factors in disease has improved our ability to predict the risk of disease in asymptomatic individuals. We have learned how to prevent the manifestations of some of these diseases, and we are developing the capacity to treat others.

Yet, much remains unknown about the benefits and risks of building an understanding of human genetic variation at the molecular level. While this information would have the potential to dramatically improve human health, the architects of the HGP realized that it also would raise a number of complex ethical, legal, and social issues. Thus, in 1990 they established the Ethical, Legal, and Social Implications (ELSI) program to anticipate and address the ethical, legal, and social issues that arise from human genetic research. This program, perhaps more than any other, has focused public attention, as well as the attention of educators, on the increasing importance of preparing citizens to understand and contribute to the ongoing public dialogue related to advances in genetics.

Ethics is the study of right and wrong, good and bad. It has to do with the actions and character of individuals, families, communities, institutions, and societies. During the last two and one-half millennia, Western philosophy has developed a variety of powerful methods and a reliable set of concepts and technical terms for studying and talking about the ethical life. Generally speaking, we apply the terms "right" and "good" to those actions and qualities that foster the interests of individuals, families, communities, institutions, and society. Here, an "interest" refers to a participant's share or participation in a situation. The terms "wrong" or "bad" apply to those actions and qualities that impair interests.

Ethical considerations are complex, multifaceted, and raise many questions. Often, there are competing, well-reasoned answers to questions about what is right and wrong, and good and bad, about an individual's or group's conduct or actions. Typically, these answers all involve appeals to values. A value is something that has significance or worth in a given situation. One of the exciting events to witness in any discussion in ethics is the varying ways in which the individuals involved assign values to things, persons, and states of affairs. Examples of values that students may appeal to in a discussion about ethics include autonomy, freedom, privacy, sanctity of life, religion, protecting another from harm, promoting another's good, justice, fairness, relationships, scientific knowledge, and technological progress.

Acknowledging the complex, multifaceted nature of ethical discussions is not to suggest that "anything goes." Experts generally agree on the following features of ethics. First, ethics is a process of rational inquiry. It involves posing clearly formulated questions and seeking well-reasoned answers to those questions. For example, we can ask questions about an individual's right to privacy regarding personal genetic information; we also can ask questions about the appropriateness of particular uses of gene therapy. Well-reasoned answers to such questions constitute arguments. Ethical analysis and argument, then, result from successful ethical inquiry.

Second, ethics requires a solid foundation of information and rigorous interpretation of that information. For example, one must have a solid understanding of biology to evaluate the recent decision by the Icelandic government to create a database that will contain extensive genetic and medical information about the country's citizens. A knowledge of science also is needed to discuss the ethics of genetic screening or of germ-line gene therapy. Ethics is not strictly a theoretical discipline but is concerned in vital ways with practical matters.

Third, discussions of ethical issues often lead to the identification of very different answers to questions about what is right and wrong and good and bad. This is especially true in a society such as our own, which is characterized by a diversity of perspectives and values. Consider, for example, the question of whether adolescents should be tested for late-onset genetic conditions. Genetic testing centers routinely withhold genetic tests for Huntington disease (HD) from asymptomatic patients under the age of 18. The rationale is that the condition expresses itself later in life and, at present, treatment is unavailable. Therefore, there is no immediate, physical health benefit for a minor from a specific diagnosis based on genetic testing. In addition, there is concern about the psychological effects of knowing that later in life one will get a debilitating, life-threatening condition. Teenagers can wait until they are adults to decide what and when they would like to know. In response, some argue that many adolescents and young children do have sufficient autonomy in consent and decision making and may wish to know their future. Others argue that parents should have the right to have their children tested, because parents make many other medical decisions on behalf of their children. This example illustrates how the tools of ethics can bring clarity and rigor to discussions involving values.

One of the goals of this module is to help students see how understanding science can help individuals and society make reasoned decisions about issues related to genetics and health. Activity 5, Making Decisions in the Face of Uncertainty, presents students with a case of a woman who is concerned that she may carry an altered gene that predisposes her to breast and ovarian cancer. The woman is faced with numerous decisions, which students also consider. Thus, the focus of Activity 5 is prudential decision making, which involves the ability to avoid unnecessary risk when it is uncertain whether an event actually will occur. By completing the activity, students understand that uncertainty is often a feature of questions related to genetics and health, because our knowledge of genetics is incomplete and constantly changing. In addition, students see that making decisions about an uncertain future is complex. In simple terms, students have to ask themselves, "How bad is the outcome and how likely is it to occur?" When the issues are weighed, different outcomes are possible, depending on one's estimate of the incidence of the occurrence and how much burden one attaches to the risk.

Clearly, science as well as ethics play important roles in helping individuals make choices about individual and public health. Science provides evidence that can help us understand and treat human disease, illness, deformity, and dysfunction. And ethics provides a framework for identifying and clarifying values and the choices that flow from these values. But the relationships between scientific information and human choices, and between choices and behaviors, are not straightforward. In other words, human choice allows individuals to choose against sound knowledge, and choice does not require action.

Nevertheless, it is increasingly difficult to deny the claims of science. We are continually presented with great amounts of relevant scientific and medical knowledge that is publicly accessible. As a consequence, we can think about the relationships between knowledge, choice, behavior, and human welfare in the following ways:

One of the goals of this module is to encourage students to think in terms of these relationships, now and as they grow older.

Biological Sciences Curriculum Study. Teaching tools. Dubuque, IA: Kendall/Hunt Publishing Company; 1999.

Bonwell CC, Eison JA. Washington, DC: The George Washington University: School of Education and Human Development; Active learning: Creating excitement in the classroom. 1991 (ASHE-ERIC Higher Education Report No. 1)

Brody CM. Collaborative or cooperative learning? Complementary practices for instructional reform. The Journal of Staff, Program, & Organizational Development. 1995;12(3):134143.

Harrison GA, Tanner JM, Pilbeam DR, Baker PT. Human biology: An introduction to human evolution, variation, growth, and adaptability. New York: Oxford University Press; 1988.

Knapp MS, Shields PM, Turnbull BJ. Academic challenge in high-poverty classrooms. Phi Delta Kappan. 1995;76(10):770776.

Lander ES. Array of hope. Supplement to nature genetics. 1999 January;21

Moore JA. Science as a way of knowing: The foundations of modern biology. Cambridge, MA: Harvard University Press; 1993.

National Institutes of Health. Congressional justification. Bethesda, MD: Author; 1996.

National Research Council. National science education standards. Washington, DC: National Academy Press; 1996.

Perkins D. Smart schools: Better thinking and learning for every child. New York: The Free Press; 1992.

Project Kaleidoscope. What works: Building natural science communities. Vol. 1. Washington, DC: Stamats Communications, Inc; 1991.

Roblyer MD, Edwards J, Havriluk MA. Integrating educational technology into teaching. Upper Saddle River, NJ: Prentice-Hall, Inc; 1997.

Saltus R. Tailor-made drugs. The Boston Globe. 1998 April 20

Saunders WL. The constructivist perspective: Implications and teaching strategies for science. School Science and Mathematics. 1992;92(3):136141.

Sizer TR. Horace's school: Redesigning the American high school. New York: Houghton Mifflin Co; 1992.

Vogel F, Motulsky AG. Human genetics: Problems and approaches. 3rd ed. New York: Springer; 1997.

The following glossary was modified from the glossary on the National Human Genome Research Institute's Web site, available at http://www.nhgri.nih.gov.

One of the variant forms of a gene at a particular locus, or location, on a chromosome. Different alleles produce variation in inherited characteristics such as hair color or blood type. In an individual, one form of the allele (the dominant one) may be expressed more than another form (the recessive one).

One of 20 different kinds of small molecules that link together in long chains to form proteins. Amino acids are referred to as the "building blocks" of proteins.

Gene on one of the autosomes that, if present, will almost always produce a specific trait or disease. The chance of passing the gene (and therefore the disease) to children is 50-50 in each pregnancy.

Chromosome other than a sex chromosome. Humans have 22 pairs of autosomes.

Two bases that form a "rung of the DNA ladder." The bases are the "letters" that spell out the genetic code. In DNA, the code letters are A, T, G, and C, which stand for the chemicals adenine, thymine, guanine, and cytosine, respectively. In base pairing, adenine always pairs with thymine, and guanine always pairs with cytosine.

Defect present at birth, whether caused by mutant genes or by prenatal events that are not genetic.

First breast cancer genes to be identified. Mutated forms of these genes are believed to be responsible for about one-half the cases of inherited breast cancer, especially those that occur in younger women, and also to increase a woman's risk for ovarian cancer. Both are tumor suppressor genes.

Diseases in which abnormal cells divide and grow unchecked. Cancer can spread from its original site to other parts of the body and can be fatal if not treated adequately.

Gene, located in a chromosome region suspected of being involved in a disease, whose protein product suggests that it could be the disease gene in question.

Mutation that confers immunity to infection by HIV. The mutation alters the structure of a receptor on the surface of macrophages such that HIV cannot enter the cell.

Collection of DNA sequences generated from mRNA sequences. This type of library contains only protein-coding DNA (genes) and does not include any noncoding DNA.

Basic unit of any living organism. It is a small, watery, compartment filled with chemicals and a complete copy of the organism's genome.

One of the thread like "packages" of genes and other DNA in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes, 46 in all: 44 autosomes and two sex chromosomes. Each parent contributes one chromosome to each pair, so children get one-half of their chromosomes from their mothers and one-half from their fathers.

Process of making copies of a specific piece of DNA, usually a gene. When geneticists speak of cloning, they do not mean the process of making genetically identical copies of an entire organism.

Three bases in a DNA or RNA sequence that specify a single amino acid.

Hereditary disease whose symptoms usually appear shortly after birth. They include faulty digestion, breathing difficulties and respiratory infections due to mucus accumulation, and excessive loss of salt in sweat. In the past, cystic fibrosis was almost always fatal in childhood, but treatment is now so improved that patients commonly live to their 20s and beyond.

Visual appearance of a chromo some when stained and examined under a microscope. Particularly important are visually distinct regions, called light and dark bands, that give each of the chromosomes a unique appearance. This feature allows a person's chromosomes to be studied in a clinical test known as a karyotype, which allows scientists to look for chromosomal alterations.

Particular kind of mutation: loss of a piece of DNA from a chromosome. Deletion of a gene or part of a gene can lead to a disease or abnormality.

Chemical inside the nucleus of a cell that carries the genetic instructions for making living organisms.

Number of chromosomes in most cells except the gametes. In humans, the diploid number is 46.

Technology that identifies mutations in genes. It uses small glass plates that contain synthetic single-stranded DNA sequences identical to those of a normal gene.

Process by which the DNA double helix unwinds and makes an exact copy of itself.

Determining the exact order of the base pairs in a segment of DNA.

Gene that almost always results in a specific physical characteristic (for example, a disease) even though the patient's genome possesses only one copy. With a dominant gene, the chance of passing on the gene (and therefore the disease) to children is 50-50 in each pregnancy.

Structural arrangement of DNA, which looks something like an immensely long ladder twisted into a helix, or coil. The sides of the "ladder" are formed by a backbone of sugar and phosphate molecules, and the "rungs" consist of nucleotide bases joined weakly in the middle by hydrogen bonds.

Particular kind of mutation: production of one or more copies of any piece of DNA, including a gene or even an entire chromosome.

Process in which molecules (such as proteins, DNA, or RNA fragments) can be separated according to size and electrical charge by applying an electric current to them. The current forces the molecules through pores in a thin layer of gel, a firm, jellylike substance. The gel can be made so that its pores are just the right dimensions for separating molecules within a specific range of sizes and shapes. Smaller fragments usually travel further than large ones. The process is sometimes called gel electrophoresis.

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The The Journal of Human Genetics is the official journal of the Japan Society of Human Genetics, publishing high-quality original research articles, short communications, reviews, correspondences and editorials on all aspects of human genetics and genomics. It is the leading genetics journal based in the Asia-Pacific region.

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Cardiovascular Genetics

Genetics studies help elucidating mechanisms of Cardiovascular Diseases (CVDs). The new JHG web focus features CVDs with 11 special articles introducing latest studies around CVDs. Topics such as genetics of congenial heart disease, hereditary large vessel diseases and cardiomyopathy are discussed.

Announcing the winners of 2015 JHG Young Scientist Award

JSHG - Journal of Human Genetics Young Scientist Award identifies articles that have made a significant contribution to the Journal of Human Genetics, using the judgment criterion of scientific excellence and impact in the field of human genetics.

Shinji Ono Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familial infantile convulsionsFREE

Surakameth Mahasirimongkol Genome-wide association studies of tuberculosis in Asians identify distinct at-risk locus for young tuberculosisFREE

Web Focus: Reviews in JHG

Welcome to the JHG Reviews collection - a selection of recently published Reviews on various topics in Human Genetics studies. This collection is freely available until January 2016 and features some important articles from the past collection of reviews on pharmacogenomics and epidemiology, or comprehensive review on the impact of whole-exome sequencing.

Editor's Choice- Highly-Influential Articles in Human Genetics

This Editor's Choice web focus presents a range of research papers and review articles on popular topics in human genetics, including next generation sequencing (NGS), the molecular basis of genetic diseases, and population genetics all drawn from the pages of the Journal of Human Genetics (JHG).

JHG Commentaries and commented articles

The Journal of Human Genetics is delighted to feature Commentaries, which provide narratives of interpretation, evaluation and opinion from area experts about the topics discussed in articles appeared in the same or recent issues of the journal. This web focus provides you with free access to a selected set of commentary and commented articles published from recent issues. You are invited to view full text of these articles and check how research experts have described and commented on these original articles, and how their comments may differ from your own thoughts and opinions.

JHG Archive 1977-2005

We are happy to announce that the archive of the The Journal of Human Genetics from 1977-2005 is now freely available in our Archive.

Research Diversity web focus

The Journal of Human Genetics (JHG) is pleased to presents fine articles and reviews on various aspects of human genetics on the JHG research diversity. Selected papers include the first genome-wide association study on anorexia nervosa, review and article on recent progress in asthma genetics, articles on new associations with schizophrenia, hair thickness etc.

Editor's choice

The Journal of Human Genetics is proud to present a collection of top reviews from recent years, as chosen by the editor. This collection covers a range of topics, including the functional analysis of disease-causing genes, polymorphisms of disease-associated genes, statistical genetics, pharmacogenetics, medical genetics and the genetics of multifactorial disease. Complementing this collection, the January issue also includes the latest reviews and articles on various aspects of human genetics.

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From January 2009, Nature Publishing Group begins publishing the Journal of Human Genetics on behalf of the Japan Society of Human Genetics.

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Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA (the DNA contained in human mitochondria). The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell.

Mitochondrial DNA (mtDNA) is not transmitted through nuclear DNA (nDNA). In humans, as in most multicellular organisms, mitochondrial DNA is inherited only from the mother's ovum. There are theories, however, that paternal mtDNA transmission in humans can occur under certain circumstances.[1]

Mitochondrial inheritance is therefore non-Mendelian, as Mendelian inheritance presumes that half the genetic material of a fertilized egg (zygote) derives from each parent.

Eighty percent of mitochondrial DNA codes for mitochondrial RNA, and therefore most mitochondrial DNA mutations lead to functional problems, which may be manifested as muscle disorders (myopathies).

Because they provide 30 molecules of ATP per glucose molecule in contrast to the 2 ATP molecules produced by glycolysis, mitochondria are essential to all higher organisms for sustaining life. The mitochondrial diseases are genetic disorders carried in mitochondrial DNA, or nuclear DNA coding for mitochondrial components. Slight problems with any one of the numerous enzymes used by the mitochondria can be devastating to the cell, and in turn, to the organism.

In humans, mitochondrial DNA (mtDNA) forms closed circular molecules that contain 16,569,[2][3] DNA base pairs,[4] with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules, with the quantity ranging between 1 and 15.[4] Each human cell contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500.[4]

Because mitochondrial diseases (diseases due to malfunction of mitochondria) can be inherited both maternally and through chromosomal inheritance, the way in which they are passed on from generation to generation can vary greatly depending on the disease. Mitochondrial genetic mutations that occur in the nuclear DNA can occur in any of the chromosomes (depending on the species). Mutations inherited through the chromosomes can be autosomal dominant or recessive and can also be sex-linked dominant or recessive. Chromosomal inheritance follows normal Mendelian laws, despite the fact that the phenotype of the disease may be masked.

Because of the complex ways in which mitochondrial and nuclear DNA "communicate" and interact, even seemingly simple inheritance is hard to diagnose. A mutation in chromosomal DNA may change a protein that regulates (increases or decreases) the production of another certain protein in the mitochondria or the cytoplasm; this may lead to slight, if any, noticeable symptoms. On the other hand, some devastating mtDNA mutations are easy to diagnose because of their widespread damage to muscular, neural, and/or hepatic tissues (among other high-energy and metabolism-dependent tissues) and because they are present in the mother and all the offspring.

Mitochondrial genome mutations are passed on 100% of the time from mother to all her offspring. So, if a female has a mitochondrial trait, all offspring inherit it. However, if a male has a mitochondrial trait, no offspring inherit it. The number of affected mtDNA molecules inherited by a specific offspring can vary greatly because

It is possible, even in twin births, for one baby to receive more than half mutant mtDNA molecules while the other twin may receive only a tiny fraction of mutant mtDNA molecules with respect to wildtype (depending on how the twins divide from each other and how many mutant mitochondria happen to be on each side of the division). In a few cases, some mitochondria or a mitochondrion from the sperm cell enters the oocyte but paternal mitochondria are actively decomposed.

Genes in the human mitochondrial genome are as follows.

It was originally incorrectly believed that the mitochondrial genome contained only 13 protein-coding genes, all of them encoding proteins of the electron transport chain. However, in 2001, a 14th biologically active protein called humanin was discovered, and was found to be encoded by the mitochondrial gene MT-RNR2 which also encodes part of the mitochondrial ribosome (made out of RNA):

Unlike the other proteins, humanin does not remain in the mitochondria, and interacts with the rest of the cell and cellular receptors. Humanin can protect brain cells by inhibiting apoptosis. Despite its name, versions of humanin also exist in other animals, such as rattin in rats.

Mitochondrial rRNA is encoded by MT-RNR1 (12S) and MT-RNR2 (16S).

The following genes encode tRNA:

In humans, the light strand of mtDNA carries 28 genes and the heavy strand of mtDNA carries only 9 genes.[5] Eight of the 9 genes on the heavy strand code for mitochondrial tRNA molecules. Human mtDNA consists of 16,569 nucleotide pairs. The entire molecule is regulated by only one regulatory region which contains the origins of replication of both heavy and light strands. The entire human mitochondrial DNA molecule has been mapped[1][2].

The genetic code is, for the most part, universal, with few exceptions: mitochondrial genetics includes some of these. For most organisms the "stop codons" are "UAA", "UAG", and "UGA". In vertebrate mitochondria "AGA" and "AGG" are also stop codons, but not "UGA", which codes for tryptophan instead. "AUA" codes for isoleucine in most organisms but for methionine in vertebrate mitochondrial mRNA.

There are many other variations among the codes used by other mitochondrial m/tRNA, which happened not to be harmful to their organisms, and which can be used as a tool (along with other mutations among the mtDNA/RNA of different species) to determine relative proximity of common ancestry of related species. (The more related two species are, the more mtDNA/RNA mutations will be the same in their mitochondrial genome).

Using these techniques, it is estimated that the first mitochondria arose around 1.5 billion years ago. A generally accepted hypothesis is that mitochondria originated as an aerobic prokaryote in a symbiotic relationship within an anaerobic eukaryote.

Mitochondrial replication is controlled by nuclear genes and is specifically suited to make as many mitochondria as that particular cell needs at the time.

Mitochondrial transcription in Human is initiated from three promoters, H1, H2, and L (heavy strand 1, heavy strand 2, and light strand promoters). The H2 promoter transcribes almost the entire heavy strand and the L promoter transcribes the entire light strand. The H1 promoter causes the transcription of the two mitochondrial rRNA molecules.[6]

When transcription takes place on the heavy strand a polycistronic transcript is created. The light strand produces either small transcripts, which can be used as primers, or one long transcript. The production of primers occurs by processing of light strand transcripts with the Mitochondrial RNase MRP (Mitochondrial RNA Processing). The requirement of transcription to produce primers links the process of transcription to mtDNA replication. Full length transcripts are cut into functional tRNA, rRNA, and mRNA molecules.[citation needed]

The process of transcription initiation in mitochondria involves three types of proteins: the mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factors B1 and B2 (TFB1M, TFB2M). POLRMT, TFAM, and TFB1M or TFB2M assemble at the mitochondrial promoters and begin transcription. The actual molecular events that are involved in initiation are unknown, but these factors make up the basal transcription machinery and have been shown to function in vitro.[citation needed]

Mitochondrial translation is still not very well understood. In vitro translations have still not been successful, probably due to the difficulty of isolating sufficient mt mRNA, functional mt rRNA, and possibly because of the complicated changes that the mRNA undergoes before it is translated.[citation needed]

The Mitochondrial DNA Polymerase (Pol gamma, encoded by the POLG gene) is used in the copying of mtDNA during replication. Because the two (heavy and light) strands on the circular mtDNA molecule have different origins of replication, it replicates in a D-loop mode. One strand begins to replicate first, displacing the other strand. This continues until replication reaches the origin of replication on the other strand, at which point the other strand begins replicating in the opposite direction. This results in two new mtDNA molecules. Each mitochondrion has several copies of the mtDNA molecule and the number of mtDNA molecules is a limiting factor in mitochondrial fission. After the mitochondrion has enough mtDNA, membrane area, and membrane proteins, it can undergo fission (very similar to that which bacteria use) to become two mitochondria. Evidence suggests that mitochondria can also undergo fusion and exchange (in a form of crossover) genetic material among each other. Mitochondria sometimes form large matrices in which fusion, fission, and protein exchanges are constantly occurring. mtDNA shared among mitochondria (despite the fact that they can undergo fusion).[citation needed]

Mitochondrial DNA is susceptible to damage from free oxygen radicals from mistakes that occur during the production of ATP through the electron transport chain. These mistakes can be caused by genetic disorders, cancer, and temperature variations. These radicals can damage mtDNA molecules or change them, making it hard for mitochondrial polymerase to replicate them. Both cases can lead to deletions, rearrangements, and other mutations. Recent evidence has suggested that mitochondria have enzymes that proofread mtDNA and fix mutations that may occur due to free radicals. It is believed that a DNA recombinase found in mammalian cells is also involved in a repairing recombination process. Deletions and mutations due to free radicals have been associated with the aging process. It is believed that radicals cause mutations which lead to mutant proteins, which in turn led to more radicals. This process takes many years and is associated with some aging processes involved in oxygen-dependent tissues such as brain, heart, muscle, and kidney. Auto-enhancing processes such as these are possible causes of degenerative diseases including Parkinson's, Alzheimer's, and coronary artery disease.[citation needed]

Because mitochondrial growth and fission are mediated by the nuclear DNA, mutations in nuclear DNA can have a wide array of effects on mtDNA replication. Despite the fact that the loci for some of these mutations have been found on human chromosomes, specific genes and proteins involved have not yet been isolated. Mitochondria need a certain protein to undergo fission. If this protein (generated by the nucleus) is not present, the mitochondria grow but they do not divide. This leads to giant, inefficient mitochondria. Mistakes in chromosomal genes or their products can also affect mitochondrial replication more directly by inhibiting mitochondrial polymerase and can even cause mutations in the mtDNA directly and indirectly. Indirect mutations are most often caused by radicals created by defective proteins made from nuclear DNA.[citation needed]

In total, the mitochondrion hosts about 3000 different types of proteins, but only about 13 of them are coded on the mitochondrial DNA. Most of the 3000 types of proteins are involved in a variety of processes other than ATP production, such as porphyrin synthesis. Only about 3% of them code for ATP production proteins. This means most of the genetic information coding for the protein makeup of mitochondria is in chromosomal DNA and is involved in processes other than ATP synthesis. This increases the chances that a mutation that will affect a mitochondrion will occur in chromosomal DNA, which is inherited in a Mendelian pattern. Another result is that a chromosomal mutation will affect a specific tissue due to its specific needs, whether those may be high energy requirements or a need for the catabolism or anabolism of a specific neurotransmitter or nucleic acid. Because several copies of the mitochondrial genome are carried by each mitochondrion (2-10 in humans), mitochondrial mutations can be inherited maternally by mtDNA mutations which are present in mitochondria inside the oocyte before fertilization, or (as stated above) through mutations in the chromosomes.[citation needed]

Mitochondrial diseases range in severity from asymptomatic to fatal, and are most commonly due to inherited rather than acquired mutations of mitochondrial DNA. A given mitochondrial mutation can cause various diseases depending on the severity of the problem in the mitochondria and the tissue the affected mitochondria are in. Conversely, several different mutations may present themselves as the same disease. This almost patient-specific characterization of mitochondrial diseases (see Personalized medicine) makes them very hard to accurately recognize, diagnose and trace. Some diseases are observable at or even before birth (many causing death) while others do not show themselves until late adulthood (late-onset disorders). This is because the number of mutant versus wildtype mitochondria varies between cells and tissues, and is continuously changing. Because cells have multiple mitochondria, different mitochondria in the same cell can have different variations of the mtDNA. This condition is referred to as heteroplasmy. When a certain tissue reaches a certain ratio of mutant versus wildtype mitochondria, a disease will present itself. The ratio varies from person to person and tissue to tissue (depending on its specific energy, oxygen, and metabolism requirements, and the effects of the specific mutation). Mitochondrial diseases are very numerous and different. Apart from diseases caused by abnormalities in mitochondrial DNA, many diseases are suspected to be associated in part by mitochondrial dysfunctions, such as diabetes mellitus, forms of cancer and cardiovascular disease, lactic acidosis, specific forms of myopathy, osteoporosis, Alzheimer's disease, Parkinsons's disease, stroke, male infertility and which are also believed to play a role in the aging process.[citation needed]

Human mtDNA can also be used to help identify individuals.[7] Forensic laboratories occasionally use mtDNA comparison to identify human remains, and especially to identify older unidentified skeletal remains. Although unlike nuclear DNA, mtDNA is not specific to one individual, it can be used in combination with other evidence (anthropological evidence, circumstantial evidence, and the like) to establish identification. mtDNA is also used to exclude possible matches between missing persons and unidentified remains.[8] Many researchers believe that mtDNA is better suited to identification of older skeletal remains than nuclear DNA because the greater number of copies of mtDNA per cell increases the chance of obtaining a useful sample, and because a match with a living relative is possible even if numerous maternal generations separate the two. American outlaw Jesse James's remains were identified using a comparison between mtDNA extracted from his remains and the mtDNA of the son of the female-line great-granddaughter of his sister.[9] Similarly, the remains of Alexandra Feodorovna (Alix of Hesse), last Empress of Russia, and her children were identified by comparison of their mitochondrial DNA with that of Prince Philip, Duke of Edinburgh, whose maternal grandmother was Alexandra's sister Victoria of Hesse.[10] Similarly to identify Emperor Nicholas II remains his mitochondrial DNA was compared with that of James Carnegie, 3rd Duke of Fife, whose maternal great-grandmother Alexandra of Denmark (Queen Alexandra) was sister of Nicholas II mother Dagmar of Denmark (Empress Maria Feodorovna).[11]

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Explore traits, the characteristics that make us unique.

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These vehicles of inheritance pack a lot of information.

Funding provided by a gift from the R. Harold Burton Foundation.

APA format: Genetic Science Learning Center (2014, June 22) Tour of Basic Genetics. Learn.Genetics. Retrieved July 10, 2016, from http://learn.genetics.utah.edu/content/basics/ MLA format: Genetic Science Learning Center. "Tour of Basic Genetics." Learn.Genetics 10 July 2016 <http://learn.genetics.utah.edu/content/basics/> Chicago format: Genetic Science Learning Center, "Tour of Basic Genetics," Learn.Genetics, 22 June 2014, <http://learn.genetics.utah.edu/content/basics/> (10 July 2016)

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Tour of Basic Genetics

The Department of Human Genetics is dedicated to basic scientific research in human genetics and genetic disease, as well as the training of the next generation of scientists and health care providers.

Our faculty explore three broad areas of human genetics: molecular genetics, genetic disease, and statistical/population genetics. Within molecular genetics, research groups study DNA repair and recombination, genome instability, gene function and regulation, epigenetics, RNA modification and control, and genomic systems. Research in human genetic disease emphasizes the genetics of development, neurogenetics, stem cell biology, medical genetics, reproductive sciences, and the genetics of cancer. Evolutionary and population genetics research includes statistical tools for genetics, genetic epidemiology, and genetic mapping of complex traits and diseases.

We invite you to explore our faculty, students, graduate programs, courses, and events/seminars.

Wildschutte JH, Williams ZH, Montesion M, Subramanian RP, Kidd JM, Coffin JM. Discovery of unfixed endogenous retrovirus insertions in diverse human populations. Published online PNAS March 21, 2016 http://www.pnas.org/content/early/2016/03/16/1602336113

Iwase S, Brookes E, Agarwal S, Badeaux AI, Ito H, Vallianatos CN, Tomassy GS, Kasza T, Lin G, Thompson A, Gu L, Kwan KY, Chen C, Sartor MA, Egan B, Xu J, Shi Y. A mouse model of X-linked intellectual disability associated with impaired removal of histone methylation. Cell Rep. 2016 Feb 9;14(5):1000-9. [PubMed]

Lenk GM, Frei CM, Miller AC, Wallen RC, Mironova YA, Giger RJ, Meisler MH. Rescue of neurodegeneration in the Fig4 null mouse by a catalytically inactive FIG4 transgene. Hum Mol Genet. 2016 Jan 15;25(2):340-7. [PubMed]

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The Genomics Landscape The Power of Model Organisms for Studying Rare Diseases In this issue of The Genomics Landscape, we feature the use of model organisms to explore the function of genes implicated in human disease. This month's issue also highlights a recently completed webinar series to help professionals in the health insurance industry understand genetic testing, new funding for training in genomic medicine research, and NHGRI's Genome Statute and Legislation Database. Read more New training grants prime doctors to tackle genomic medicine The practice of medicine is expensive and doesn't fit in a one-hour time frame. Tests can only eliminate one diagnosis at a time. Questioning and family history can help a doctor arrive at the correct diagnosis, but even with the information gathered upfront, there are a huge number of tests to consider, and many tests may still be needed. Training doctors to use genomic sequencing is a powerful solution to the challenges facing today's medical practice. Read more One little fish hooks genome researchers with its versatility Modern molecular biology and the genome of a tiny silver and black striped fish - the zebrafish - are making waves in genomics research. This tiny fish is a powerhouse tool that helps researchers better understand the genes that are implicated in disease. Here, at the National Human Genome Research Institute (NHGRI), researchers are working to advance human health by coupling the potential of this little fish with an institute-funded resource known as The Zebrafish Core. Read more New NIH studies seek adults and families affected by sickle cell disease/trait People with sickle cell disease (SCD) can experience excruciating pain, kidney problems, a higher risk of stroke and, in rare cases, chronic leg ulcers. Little is known about why the severity of these symptoms varies throughout a lifetime or why these symptoms differ from person to person. NHGRI researchers are seeking help from people affected by SCD to find the factors - environmental, social and genetic - that impact the severity of the symptoms. Read more Video now available The Genomic Landscape of Breast Cancer in Women of African Ancestry On June 7, Olufunmilayo I. Olopade, M.D., F.A.C.P., presented The Genomic Landscape of Breast Cancer in Women of African Ancestry, the final lecture in the 2016 Genomics and Health Disparities Lecture Series. Dr. Olufunmilayo is director of the Center for Clinical Cancer Genetics at the University of Chicago School of Medicine. She is an expert in cancer risk assessment and treatment for aggressive forms of breast cancer. Watch video | Read about the series

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