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The Division of Human Genetics provides comprehensive inpatient, outpatient and laboratory genetic services to patients of all ages, including a network of statewide outreach clinics.

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Services | Patient Conditions | Comprehensive Evaluations | Special Programs | Diagnostic Laboratories | Services to Physicians

Through their Genetics Services, The University of Maryland Childrens Hospital offers a number of resources for patients seeking genetic evaluation, genetic counseling and testing.

The Childrens Hospital has biochemical genetics and cytogenetics laboratory testing on-site, as well as close relationships with DNA and other diagnostic labs around the country.

Genetic disorders

Birth defects

Multiple malformation syndromes

Pregnancy with genetic high-risk factors

Suspected fetal anomalies

Biochemical genetics: comprehensive testing for inborn errors of metabolism; quantitative amino acid and organic acid analysis, mucopolysaccharide and oligosaccharide screening, assays for 18 different lysosomal enzymes, carnitine, biotinidase, enzymes and metabolites involved in galactosemia; carrier screening for Tay-Sachsand other disorders routinely offered

Cytogenetics: routine banding and fluorescence in situ hybridization analysis of amniotic fluid, chorionic villi, peripheral blood, bone marrow, products of conception and solid tumors

Molecular genetics: DNA-based testing for fragile X syndrome, cystic fibrosis, Tay-Sachs, Gaucher disease, Canavan disease, Factor V Leiden; other testing arranged on request

Prenatal Screening: Maternal serum multiple marker screening (AFP, estriol, and hCG) for fetal neural tube defects and fetal Down's syndrome

Comprehensive genetic evaluation

Consultation on complicated cases

Second opinions

Special treatment procedures

Short-term and long-term management

State-of-the-art genetic laboratory service

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Genetics, chromosomeCreated and produced by QA International. QA International, 2010. All rights reserved. http://www.qa-international.comstudy of heredity in general and of genes in particular. Genetics forms one of the central pillars of biology and overlaps with many other areas such as agriculture, medicine, and biotechnology.

Since the dawn of civilization, humankind has recognized the influence of heredity and has applied its principles to the improvement of cultivated crops and domestic animals. A Babylonian tablet more than 6,000 years old, for example, shows pedigrees of horses and indicates possible inherited characteristics. Other old carvings show cross-pollination of date palm trees. Most of the mechanisms of heredity, however, remained a mystery until the 19th century, when genetics as a systematic science began.

Crick, Francis Harry Compton: proposed DNA structureEncyclopdia Britannica, Inc.Genetics arose out of the identification of genes, the fundamental units responsible for heredity. Genetics may be defined as the study of genes at all levels, including the ways in which they act in the cell and the ways in which they are transmitted from parents to offspring. Modern genetics focuses on the chemical substance that genes are made of, called deoxyribonucleic acid, or DNA, and the ways in which it affects the chemical reactions that constitute the living processes within the cell. Gene action depends on interaction with the environment. Green plants, for example, have genes containing the information necessary to synthesize the photosynthetic pigment chlorophyll that gives them their green colour. Chlorophyll is synthesized in an environment containing light because the gene for chlorophyll is expressed only when it interacts with light. If a plant is placed in a dark environment, chlorophyll synthesis stops because the gene is no longer expressed.

Genetics as a scientific discipline stemmed from the work of Gregor Mendel in the middle of the 19th century. Mendel suspected that traits were inherited as discrete units, and, although he knew nothing of the physical or chemical nature of genes at the time, his units became the basis for the development of the present understanding of heredity. All present research in genetics can be traced back to Mendels discovery of the laws governing the inheritance of traits. The word genetics was introduced in 1905 by English biologist William Bateson, who was one of the discoverers of Mendels work and who became a champion of Mendels principles of inheritance.

Although scientific evidence for patterns of genetic inheritance did not appear until Mendels work, history shows that humankind must have been interested in heredity long before the dawn of civilization. Curiosity must first have been based on human family resemblances, such as similarity in body structure, voice, gait, and gestures. Such notions were instrumental in the establishment of family and royal dynasties. Early nomadic tribes were interested in the qualities of the animals that they herded and domesticated and, undoubtedly, bred selectively. The first human settlements that practiced farming appear to have selected crop plants with favourable qualities. Ancient tomb paintings show racehorse breeding pedigrees containing clear depictions of the inheritance of several distinct physical traits in the horses. Despite this interest, the first recorded speculations on heredity did not exist until the time of the ancient Greeks; some aspects of their ideas are still considered relevant today.

Hippocrates (c. 460c. 375 bce), known as the father of medicine, believed in the inheritance of acquired characteristics, and, to account for this, he devised the hypothesis known as pangenesis. He postulated that all organs of the body of a parent gave off invisible seeds, which were like miniaturized building components and were transmitted during sexual intercourse, reassembling themselves in the mothers womb to form a baby.

Aristotle (384322 bce) emphasized the importance of blood in heredity. He thought that the blood supplied generative material for building all parts of the adult body, and he reasoned that blood was the basis for passing on this generative power to the next generation. In fact, he believed that the males semen was purified blood and that a womans menstrual blood was her equivalent of semen. These male and female contributions united in the womb to produce a baby. The blood contained some type of hereditary essences, but he believed that the baby would develop under the influence of these essences, rather than being built from the essences themselves.

Aristotles ideas about the role of blood in procreation were probably the origin of the still prevalent notion that somehow the blood is involved in heredity. Today people still speak of certain traits as being in the blood and of blood lines and blood ties. The Greek model of inheritance, in which a teeming multitude of substances was invoked, differed from that of the Mendelian model. Mendels idea was that distinct differences between individuals are determined by differences in single yet powerful hereditary factors. These single hereditary factors were identified as genes. Copies of genes are transmitted through sperm and egg and guide the development of the offspring. Genes are also responsible for reproducing the distinct features of both parents that are visible in their children.

In the two millennia between the lives of Aristotle and Mendel, few new ideas were recorded on the nature of heredity. In the 17th and 18th centuries the idea of preformation was introduced. Scientists using the newly developed microscopes imagined that they could see miniature replicas of human beings inside sperm heads. French biologist Jean-Baptiste Lamarck invoked the idea of the inheritance of acquired characters, not as an explanation for heredity but as a model for evolution. He lived at a time when the fixity of species was taken for granted, yet he maintained that this fixity was only found in a constant environment. He enunciated the law of use and disuse, which states that when certain organs become specially developed as a result of some environmental need, then that state of development is hereditary and can be passed on to progeny. He believed that in this way, over many generations, giraffes could arise from deerlike animals that had to keep stretching their necks to reach high leaves on trees.

British naturalist Alfred Russel Wallace originally postulated the theory of evolution by natural selection. However, Charles Darwins observations during his circumnavigation of the globe aboard the HMS Beagle (183136) provided evidence for natural selection and his suggestion that humans and animals shared a common ancestry. Many scientists at the time believed in a hereditary mechanism that was a version of the ancient Greek idea of pangenesis, and Darwins ideas did not appear to fit with the theory of heredity that sprang from the experiments of Mendel.

Before Gregor Mendel, theories for a hereditary mechanism were based largely on logic and speculation, not on experimentation. In his monastery garden, Mendel carried out a large number of cross-pollination experiments between variants of the garden pea, which he obtained as pure-breeding lines. He crossed peas with yellow seeds to those with green seeds and observed that the progeny seeds (the first generation, F1) were all yellow. When the F1 individuals were self-pollinated or crossed among themselves, their progeny (F2) showed a ratio of 3:1 (3/4 yellow and 1/4 green). He deduced that, since the F2 generation contained some green individuals, the determinants of greenness must have been present in the F1 generation, although they were not expressed because yellow is dominant over green. From the precise mathematical 3:1 ratio (of which he found several other examples), he deduced not only the existence of discrete hereditary units (genes) but also that the units were present in pairs in the pea plant and that the pairs separated during gamete formation. Hence, the two original lines of pea plants were proposed to be YY (yellow) and yy (green). The gametes from these were Y and y, thereby producing an F1 generation of Yy that were yellow in colour because of the dominance of Y. In the F1 generation, half the gametes were Y and the other half were y, making the F2 generation produced from random mating 1/4 Yy, 1/2 YY, and 1/4 yy, thus explaining the 3:1 ratio. The forms of the pea colour genes, Y and y, are called alleles.

Mendel also analyzed pure lines that differed in pairs of characters, such as seed colour (yellow versus green) and seed shape (round versus wrinkled). The cross of yellow round seeds with green wrinkled seeds resulted in an F1 generation that were all yellow and round, revealing the dominance of the yellow and round traits. However, the F2 generation produced by self-pollination of F1 plants showed a ratio of 9:3:3:1 (9/16 yellow round, 3/16 yellow wrinkled, 3/16 green round, and 1/16 green wrinkled; note that a 9:3:3:1 ratio is simply two 3:1 ratios combined). From this result and others like it, he deduced the independent assortment of separate gene pairs at gamete formation.

Mendels success can be attributed in part to his classic experimental approach. He chose his experimental organism well and performed many controlled experiments to collect data. From his results, he developed brilliant explanatory hypotheses and went on to test these hypotheses experimentally. Mendels methodology established a prototype for genetics that is still used today for gene discovery and understanding the genetic properties of inheritance.

Mendels genes were only hypothetical entities, factors that could be inferred to exist in order to explain his results. The 20th century saw tremendous strides in the development of the understanding of the nature of genes and how they function. Mendels publications lay unmentioned in the research literature until 1900, when the same conclusions were reached by several other investigators. Then there followed hundreds of papers showing Mendelian inheritance in a wide array of plants and animals, including humans. It seemed that Mendels ideas were of general validity. Many biologists noted that the inheritance of genes closely paralleled the inheritance of chromosomes during nuclear divisions, called meiosis, that occur in the cell divisions just prior to gamete formation.

heredity: sex-linked inheritance in Drosophila fliesEncyclopdia Britannica, Inc.It seemed that genes were parts of chromosomes. In 1910 this idea was strengthened through the demonstration of parallel inheritance of certain Drosophila (a type of fruit fly) genes on sex-determining chromosomes by American zoologist and geneticist Thomas Hunt Morgan. Morgan and one of his students, Alfred Henry Sturtevant, showed not only that certain genes seemed to be linked on the same chromosome but that the distance between genes on the same chromosome could be calculated by measuring the frequency at which new chromosomal combinations arose (these were proposed to be caused by chromosomal breakage and reunion, also known as crossing over). In 1916 another student of Morgans, Calvin Bridges, used fruit flies with an extra chromosome to prove beyond reasonable doubt that the only way to explain the abnormal inheritance of certain genes was if they were part of the extra chromosome. American geneticist Hermann Joseph Mller showed that new alleles (called mutations) could be produced at high frequencies by treating cells with X-rays, the first demonstration of an environmental mutagenic agent (mutations can also arise spontaneously). In 1931 American botanist Harriet Creighton and American scientist Barbara McClintock demonstrated that new allelic combinations of linked genes were correlated with physically exchanged chromosome parts.

In 1908 British physician Archibald Garrod proposed the important idea that the human disease alkaptonuria, and certain other hereditary diseases, were caused by inborn errors of metabolism, suggesting for the first time that linked genes had molecular action at the cell level. Molecular genetics did not begin in earnest until 1941 when American geneticist George Beadle and American biochemist Edward Tatum showed that the genes they were studying in the fungus Neurospora crassa acted by coding for catalytic proteins called enzymes. Subsequent studies in other organisms extended this idea to show that genes generally code for proteins. Soon afterward, American bacteriologist Oswald Avery, Canadian American geneticist Colin M. MacLeod, and American biologist Maclyn McCarty showed that bacterial genes are made of DNA, a finding that was later extended to all organisms.

DNAEncyclopdia Britannica, Inc.A major landmark was attained in 1953 when American geneticist and biophysicist James D. Watson and British biophysicists Francis Crick and Maurice Wilkins devised a double helix model for DNA structure. This model showed that DNA was capable of self-replication by separating its complementary strands and using them as templates for the synthesis of new DNA molecules. Each of the intertwined strands of DNA was proposed to be a chain of chemical groups called nucleotides, of which there were known to be four types. Because proteins are strings of amino acids, it was proposed that a specific nucleotide sequence of DNA could contain a code for an amino acid sequence and hence protein structure. In 1955 American molecular biologist Seymour Benzer, extending earlier studies in Drosophila, showed that the mutant sites within a gene could be mapped in relation to each other. His linear map indicated that the gene itself is a linear structure.

In 1958 the strand-separation method for DNA replication (called the semiconservative method) was demonstrated experimentally for the first time by American molecular biologist Matthew Meselson and American geneticist Franklin W. Stahl. In 1961 Crick and South African biologist Sydney Brenner showed that the genetic code must be read in triplets of nucleotides, called codons. American geneticist Charles Yanofsky showed that the positions of mutant sites within a gene matched perfectly the positions of altered amino acids in the amino acid sequence of the corresponding protein. In 1966 the complete genetic code of all 64 possible triplet coding units (codons), and the specific amino acids they code for, was deduced by American biochemists Marshall Nirenberg and Har Gobind Khorana. Subsequent studies in many organisms showed that the double helical structure of DNA, the mode of its replication, and the genetic code are the same in virtually all organisms, including plants, animals, fungi, bacteria, and viruses. In 1961 French biologist Franois Jacob and French biochemist Jacques Monod established the prototypical model for gene regulation by showing that bacterial genes can be turned on (initiating transcription into RNA and protein synthesis) and off through the binding action of regulatory proteins to a region just upstream of the coding region of the gene.

Technical advances have played an important role in the advance of genetic understanding. In 1970 American microbiologists Daniel Nathans and Hamilton Othanel Smith discovered a specialized class of enzymes (called restriction enzymes) that cut DNA at specific nucleotide target sequences. That discovery allowed American biochemist Paul Berg in 1972 to make the first artificial recombinant DNA molecule by isolating DNA molecules from different sources, cutting them, and joining them together in a test tube. These advances allowed individual genes to be cloned (amplified to a high copy number) by splicing them into self-replicating DNA molecules, such as plasmids (extragenomic circular DNA elements) or viruses, and inserting these into living bacterial cells. From these methodologies arose the field of recombinant DNA technology that presently dominates molecular genetics. In 1977 two different methods were invented for determining the nucleotide sequence of DNA: one by American molecular biologists Allan Maxam and Walter Gilbert and the other by English biochemist Fred Sanger. Such technologies made it possible to examine the structure of genes directly by nucleotide sequencing, resulting in the confirmation of many of the inferences about genes originally made indirectly.

DNA fingerprinting: polymerase chain reactionEncyclopdia Britannica, Inc.In the 1970s Canadian biochemist Michael Smith revolutionized the art of redesigning genes by devising a method for inducing specifically tailored mutations at defined sites within a gene, creating a technique known as site-directed mutagenesis. In 1983 American biochemist Kary B. Mullis invented the polymerase chain reaction, a method for rapidly detecting and amplifying a specific DNA sequence without cloning it. In the last decade of the 20th century, progress in recombinant DNA technology and in the development of automated sequencing machines led to the elucidation of complete DNA sequences of several viruses, bacteria, plants, and animals. In 2001 the complete sequence of human DNA, approximately three billion nucleotide pairs, was made public.

A time line of important milestones in the history of genetics is provided in the table.

Time line of important milestones in the history of genetics

Classical genetics, which remains the foundation for all other areas in genetics, is concerned primarily with the method by which genetic traitsclassified as dominant (always expressed), recessive (subordinate to a dominant trait), intermediate (partially expressed), or polygenic (due to multiple genes)are transmitted in plants and animals. These traits may be sex-linked (resulting from the action of a gene on the sex, or X, chromosome) or autosomal (resulting from the action of a gene on a chromosome other than a sex chromosome). Classical genetics began with Mendels study of inheritance in garden peas and continues with studies of inheritance in many different plants and animals. Today a prime reason for performing classical genetics is for gene discoverythe finding and assembling of a set of genes that affects a biological property of interest.

Cytogenetics, the microscopic study of chromosomes, blends the skills of cytologists, who study the structure and activities of cells, with those of geneticists, who study genes. Cytologists discovered chromosomes and the way in which they duplicate and separate during cell division at about the same time that geneticists began to understand the behaviour of genes at the cellular level. The close correlation between the two disciplines led to their combination.

Plant cytogenetics early became an important subdivision of cytogenetics because, as a general rule, plant chromosomes are larger than those of animals. Animal cytogenetics became important after the development of the so-called squash technique, in which entire cells are pressed flat on a piece of glass and observed through a microscope; the human chromosomes were numbered using this technique.

Today there are multiple ways to attach molecular labels to specific genes and chromosomes, as well as to specific RNAs and proteins, that make these molecules easily discernible from other components of cells, thereby greatly facilitating cytogenetics research.

bacterial genetics: use of robotsUniversity College Cork, Ireland (A Britannica Publishing Partner)Microorganisms were generally ignored by the early geneticists because they are small in size and were thought to lack variable traits and the sexual reproduction necessary for a mixing of genes from different organisms. After it was discovered that microorganisms have many different physical and physiological characteristics that are amenable to study, they became objects of great interest to geneticists because of their small size and the fact that they reproduce much more rapidly than larger organisms. Bacteria became important model organisms in genetic analysis, and many discoveries of general interest in genetics arose from their study. Bacterial genetics is the centre of cloning technology.

Viral genetics is another key part of microbial genetics. The genetics of viruses that attack bacteria were the first to be elucidated. Since then, studies and findings of viral genetics have been applied to viruses pathogenic on plants and animals, including humans. Viruses are also used as vectors (agents that carry and introduce modified genetic material into an organism) in DNA technology.

Molecular genetics is the study of the molecular structure of DNA, its cellular activities (including its replication), and its influence in determining the overall makeup of an organism. Molecular genetics relies heavily on genetic engineering (recombinant DNA technology), which can be used to modify organisms by adding foreign DNA, thereby forming transgenic organisms. Since the early 1980s, these techniques have been used extensively in basic biological research and are also fundamental to the biotechnology industry, which is devoted to the manufacture of agricultural and medical products. Transgenesis forms the basis of gene therapy, the attempt to cure genetic disease by addition of normally functioning genes from exogenous sources.

The development of the technology to sequence the DNA of whole genomes on a routine basis has given rise to the discipline of genomics, which dominates genetics research today. Genomics is the study of the structure, function, and evolutionary comparison of whole genomes. Genomics has made it possible to study gene function at a broader level, revealing sets of genes that interact to impinge on some biological property of interest to the researcher. Bioinformatics is the computer-based discipline that deals with the analysis of such large sets of biological information, especially as it applies to genomic information.

The study of genes in populations of animals, plants, and microbes provides information on past migrations, evolutionary relationships and extents of mixing among different varieties and species, and methods of adaptation to the environment. Statistical methods are used to analyze gene distributions and chromosomal variations in populations.

Population genetics is based on the mathematics of the frequencies of alleles and of genetic types in populations. For example, the Hardy-Weinberg formula, p2 + 2pq + q2 = 1, predicts the frequency of individuals with the respective homozygous dominant (AA), heterozygous (Aa), and homozygous recessive (aa) genotypes in a randomly mating population. Selection, mutation, and random changes can be incorporated into such mathematical models to explain and predict the course of evolutionary change at the population level. These methods can be used on alleles of known phenotypic effect, such as the recessive allele for albinism, or on DNA segments of any type of known or unknown function.

Human population geneticists have traced the origins and migration and invasion routes of modern humans, Homo sapiens. DNA comparisons between the present peoples on the planet have pointed to an African origin of Homo sapiens. Tracing specific forms of genes has allowed geneticists to deduce probable migration routes out of Africa to the areas colonized today. Similar studies show to what degree present populations have been mixed by recent patterns of travel.

Another aspect of genetics is the study of the influence of heredity on behaviour. Many aspects of animal behaviour are genetically determined and can therefore be treated as similar to other biological properties. This is the subject material of behaviour genetics, whose goal is to determine which genes control various aspects of behaviour in animals. Human behaviour is difficult to analyze because of the powerful effects of environmental factors, such as culture. Few cases of genetic determination of complex human behaviour are known. Genomics studies provide a useful way to explore the genetic factors involved in complex human traits such as behaviour.

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the mechanisms of human gene function and malfunction and investigating pharmaceutical and other types of treatments. Since there is a high degree of evolutionary conservation between organisms, research on model organismssuch as bacteria, fungi, and fruit flies (Drosophila)which are easier to study, often provides important insights into human gene function.

Many single-gene diseases, caused by mutant alleles of a single gene, have been discovered. Two well-characterized single-gene diseases include phenylketonuria (PKU) and Tay-Sachs disease. Other diseases, such as heart disease, schizophrenia, and depression, are thought to have more complex heredity components that involve a number of different genes. These diseases are the focus of a great deal of research that is being carried out today.

Another broad area of activity is clinical genetics, which centres on advising parents of the likelihood of their children being affected by genetic disease caused by mutant genes and abnormal chromosome structure and number. Such genetic counseling is based on examining individual and family medical records and on diagnostic procedures that can detect unexpressed, abnormal forms of genes. Counseling is carried out by physicians with a particular interest in this area or by specially trained nonphysicians.

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At the Virginia Commonwealth University Department of Human and Molecular Genetics, we understand that everyone has questions about their genetic makeup. Some of us know that a particular health condition, like cystic fibrosis, intellectual disability cancer or early heart attack runs in our family. Expectant parents may have concerns about their child having a birth defect. Often families question how to best manage a genetic condition or birth defectand where they can get help--patients and families.

When a genetic condition or birth defect happens, family members often ask:

When you have questions like these, its important to ask your doctor about them. Your doctor can help you decide if a genetic consultation would be beneficial for you or your family. Genetic evaluation and counseling can help answer some of these questions. Genetic testing is available for more than 1,500 conditions and this number is increasing rapidly.

The Department of Human and Molecular Genetics has a long standing history of providing clinical genetic, laboratory and counseling services to families in Virginia and other states. Comprehensive clinical services are available, including preconception consultation, pediatric and adult diagnostic evaluation and management, metabolic consultation and management, and cancer genetic risk assessment, counseling and testing. Services are provided by a team of medical professionals including physician geneticists, genetic counselors, nutritionist, cytogeneticists and laboratory geneticists, and other genetics support staff. Prenatal counseling and testing is available through the Department of Obstetrics and Gynecology.

Clinic locations include VCU Medical Centers Ambulatory Care Center, VCU at Stony Point, MCV Physicians at Mayland in the West End, Dalton Oncology at the Massey Cancer Center and telemedicine at the Childrens Hospital of Richmonds satelliteoffice in Fredericksburg. Monthly and quarterly satellite clinics take place in various settings in the Central Virginia. Patients and families can be referred by a health care provider or may self-refer.

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11/15/2005 6:00 PM MuseumDavid Altshuler, '86, Founding Member, and Director of the Program in Medical and Population Genetics, Broad Institute; Associate Professor, Genetics and Medicine, Harvard Medical SchoolDescription: Will genomics vanquish our most common diseases, or create a society based on vile eugenics _ or both? David Altshuler outlines these possibilities in his informal talk and conversation at the MIT Museum.

Altshuler is a self-described optimist, and sees promise in current genetic research that attempts to pinpoint why some people develop diseases like adult-onset diabetes or schizophrenia. If we can identify the precise mechanisms inside cells that go haywire in individuals with an inherited predisposition to a certain disease, then it may be possible to design drugs much more accurately. "We're searching for a culprit who committed a crime, where the culprit is a mutation in a DNA sequence that made somebody get sick '. And scientists are the detectives -- CGI: Crime Gene Investigators," says Altshuler.

Scientists have a very powerful tool in the human genome sequence, and they are quickly mapping out genes that cause diseases. But the very tools that permit insight into illness may also permit researchers to isolate genes for other human traits. And this has Altshuler musing: "How about hair loss, intelligence, criminality, athletic ability '.Should society regulate the use of genetic information in reproductive choices?" What if insurance companies gain access to individuals' genetic predictors, and use this to determine risk, and rates? "There's no federal legislation to prevent someone from shaking your hand, scraping off DNA, doing a genetic test and not hiring you or refusing to give you insurance," Altshuler points out. Ultimately, he says, it will be in the hands of the public to strike a balance between restricting the use of genetic information, and permitting its application to cure disease. About the Speaker(s): Clinical endocrinologist and human geneticist David Altshuler is one of the world's leading scientists in the study of human genetic variation and its application to disease, using tools and information from the Human Genome Project. He is a lead investigator in The SNP Consortium and the International HapMap Project, public-private partnerships that have created public maps of human genome sequence variation as a foundation for disease research. Among his discoveries is the finding of a common genetic variant that increases the risk of contracting type 2 diabetes.

He received his B.S. in 1986 from MIT; a Ph.D. in 1993 from Harvard University, and an M.D. in 1994 from Harvard Medical School; he completed his internship, residency and clinical fellowship training at Massachusetts General Hospital.Host(s): Office of the Provost, MIT MuseumTape #: T20603

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Human Genetics: Our Past and Our Future | MIT Video

One of the oldest myths in human genetics is that having blue eyes is determined by a single gene, with the allele for blue eyes recessive to the allele for non-blue eyes (green, brown, or hazel). Many people who know nothing else about genetics think that two blue-eyed parents cannot have a brown-eyed child.

The color of the iris is determined by the amount of melanin, the ratio of eumelanin (which is dark brown) to pheomelanin (which is reddish), and the way the melanin is distributed in the eye. Irises with little melanin appear blue due to scattering of light by collagen fibers in the iris. Blue, gray, green and hazel eyes are only common in people of European ancestry; other people's eyes are various shades of brown.

Many studies divide eye colors into three categories: blue (or blue and gray); green and hazel; and brown. This has been criticized as an oversimplification (Brues 1975), and eye colors have been divided into nine categories (Mackey et al. 2011) or the hue and saturation values quantified (Liu et al. 2010). Eye color can change dramatically in the first few years of life, as many babies are born with blue eyes but then develop green or brown eyes (Matheny and Dolan 1975), and changes can also occur later in life (Bito et al. 1997, Liu et al. 2010). Some people have a blue or green iris with a brown ring around the pupil (Sturm and Larsson 2009), which makes the classification of eye color even more complicated.

Davenport and Davenport (1907) were the first to suggest that blue eye color was caused by a recessive allele. They claimed that whenever both parents had blue eyes, all of the children have blue eyes, but their data actually included two hazel-eyed offspring of blue-eyed parents. The authors said "we suspect [these] to be of a blue type," whatever that means.

Hurst (1908) divided eyes into just two types, "simplex" (blues and some grays, with no pigment on the outer surface of the iris) and "duplex" (all other colors). He found the following results:

Because there are no "duplex" (non-blue-eyed) offspring of two blue-eyed parents, these data fit the model of blue eyes being caused by a recessive allele at one gene.

Holmes and Loomis (1909) criticized the earlier work, saying that eye color varies continuously, and dividing it into categories is arbitrary. Out of 52 offspring of two blue-eyed parents in their data, one had brown eyes and two had gray eyes, which does not fit the idea that blue eyes are caused by a recessive allele. Boas (1918) found an even larger number of non-blue-eyed offspring of two blue-eyed parents, 26 out of 223. Surprisingly, there don't seem to have been any parent-offspring studies of eye color since then, at least none that I could find.

A number of groups surveyed associations of single-nucleotide polymorphisms with eye color, with fairly consistent results: variation in the HERC2 and OCA2 genes, which are next to each other on chromosome 15, plays a major role in determining eye color. However, variation in at least 10 other genes, plus complicated interactions between these genes, also influences eye color (reviewed in Sturm and Larsson 2009, with more recent results in Liu et al. 2010 and Pospiech et al. 2011).

Eye color is not an example of a simple genetic trait, and blue eyes are not determined by a recessive allele at one gene. Instead, eye color is determined by variation at several different genes and the interactions between them, and this makes it possible for two blue-eyed parents to have brown-eyed children.

Bito, L. Z., A. Matheny, K. J. Cruickshanks, D. M. Nondahl, and O. B. Carino. 1997. Eye color changes past early childhood: the Louisville Twin Study. Archives of Ophthalmology 115: 659-663.

Boas, H. M. 1918. Inheritance of eye color in man. American Journal of Physical Anthropology 2: 15-20.

Brues, A. M. 1975. Rethinking human pigmentation. American Journal of Physical Anthropology 43: 387-391.

Davenport, G. C., and C. B. Davenport. 1907. Heredity of eye color in man. Science 26: 589-592.

Holmes, S. J., and H. M. Loomis. 1909. The heredity of eye color and hair color in man. Biological Bulletin 18: 5065.

Hurst, C. C. 1908. On the inheritance of eye-colour in man. Proceedings of the Royal Society of London B 80: 85-96.

Liu, F., et al. (20 co-authors). 2010. Digital quantification of human eye color highlights genetic association of three new loci. PLOS Genetics 6: e1000934.

Mackey, D. A., C. H. Wilkinson, L. S. Kearns, and A. W. Hewitt. 2011. Classification of iris colour: review and refinement of a classification schema. Clinical and Experimental Ophthalmology 39: 462-471.

Matheny, A. P., and A. B. Dolan. 1975. Changes in eye color during early childhood: sex and genetic differences. Annals of Human Biology 2: 191-196.

Pospiech, E., J. Draus-Barini, T. Kupiec, A. Wojas-Pelc, and W. Branicki. 2011. Gene-gene interactions contribute to eye colour variation in humans. Journal of Human Genetics 56: 447-455.

Sturm, R. A., and M. Larsson. 2009. Genetics of human iris colour and patterns. Pigment Cells and Melanoma Research 22: 544-562.

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Myths of Human Genetics: Eye Color - University of Delaware

Chromosomes contain the recipe for making a living thing. They are found in almost every cells nucleus and are made from strands of DNA (deoxyribonucleic acid). Segments of DNA called "genes" are the ingredients. Each gene adds a specific protein to the recipe. Proteins build, regulate and maintain your body. For instance, they build bones, enable muscles to move, control digestion, and keep your heart beating.

Two of these 46 chromosomes determine the sex of a person. A girl inherits two X-chromosomes, one from her mother and one from her father. A boy inherits one X-chromosome from his mother and a small Y-chromosome from his father.

A gene can exist in many different forms, calledalleles. For example, lets say that there is one gene which determines the color of your hair. That one gene may have many forms, or alleles: black hair, brown hair, auburn hair, red hair, blond hair, etc. You inherit one allele for each gene from your mother and one from your father.

Each of the two alleles you inherit for a gene each may be strong ("dominant") or weak ("recessive"). When an allele is dominant, it means that the physical characteristic ("trait") it codes for usually is expressed, or shown, in the living organism. You need only one dominant allele to express a dominant trait. You need two recessivealleles to show a recessive form of a trait. See the heredity diagram for tongue rolling to see how dominant and recessive alleles work.

Tongue Rolling Heredity Diagram

There are several ways the genetic code can be altered. Sometimes genes are deleted or in the wrong place on a chromosome, or pieces of genes are swapped between chromosomes. As a result, the gene may not work or may turn on in the wrong part of the body.

"Point mutations" alter the genetic code by changing the letters in the codons -- the three-symbol genetic words that specify which protein to make. This can change the protein.

Original message: SAM AND TOM ATE THE HAM

Kind of point mutation

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