Category Archives: Human Genetics

Top-line phase 2 data evaluating drug candidates for treating the rare disease phenylketonuria (PKU) was announced this morning. The study compared the efficacy of 2 strains of a non-systemically absorbed drug candidate in patients with the diagnosis.

While both strains, SYNB1618 and SYNB1934, demonstrated clinically meaningful reductions in fasting plasma phenylalanine (Phe) levels, SYNB1934 will be the candidate investigated in the anticipated 2023 phase 3 clinical trial.

The rare inherited disorder is caused by a disruption in the phenylalanine hydroxylase (PAH) gene, which helps create the enzyme necessary to break down phenylalanine. As a result the phenylalanine amino acid accumulates in the body which can be dangerous and lead to serious health problems.

These patients can experience intellectual limitations in areas of thinking, understanding and communicating as well as other major health problems.Early intervention is crucialscreening for this disease is typically done at birth.

At this time there's no cure, so patients with the condition are instructed to restrict their diet to avoid foods that can increase the phenylalanine build up, typically found in high-protein foods. However, some individuals can be less restrictive if they're taking medications that are effective for them.

PKU continues to be a very challenging disease for patients, with many in need of new treatment options, Jerry Vockley, MD, PhD, Professor of Human Genetics,University of Pittsburgh, and lead investigator on the phase 2 Synpheny-1 study said in a statement. It is very promising to see these results and the potential benefits of a new, orally administered investigational product that can meaningfully lower Phe in patients with PKU.

The Synpheny-1 study was a phase 2, open-label, 28-day clinical trial that assessed the safety, tolerability and efficacy of SYNB1618 and SYNB1934 in 20 adult patients with phenylketonuria. The primary endpoint was the change in area under the curve (AUC) of plasma levels of labeled D5-phenylalanine (D5-Phe) following a meal challenge before and after the treatment period. Investigators carefully managed the patients' dietary intake to replicate their routine protein and Phe consumption.

Each candidate's ability to mitigate Phe properly was examined as the administered dose regimen was increased over 15 days of treatment and then stayed consistent at a dose of 1x1012live cells for the second half of the treatment period. Secondary endpoints included change in fasting levels of plasma Phe from baseline, incidence of treatment-emergent adverse events (TEAEs), and the levels of additional strain-specific metabolites plasma D5-TCA and urinary D5-5A.

Patients enrolled in the study had a Phe level above 600 mol/L at screening despite treatment with diet and/or sapropterin. A total of 11 patients were included in the SYNB1618 arm and with 9 in the SYNB1934 arm. At the conclusion of the investigation, 10 patients completed the SYNB1618 arm and 5 patients completed the SYNB1934 arm.

The mean change from baseline at day 14 in fasting plasma Phe was -20% for those in SYNB1618 treatment and -34% for SYNB1934. Of the patients who completed the trial, 60% had a response greater than 20% Phe reduction by day 7 or day 14, with 6 of the 10 patients dosed with SYNB1618 and 3 of the 5 dosed with SYNB1934 meeting the criteria.

No serious adverse events were reported and the mild-moderate adverse events were predominantly gastrointestinal.

The robust plasma Phe reduction demonstrated by SYNB1934 indicates that it has potential to be a transformative treatment for patients with PKU,Aoife Brennan, MB, ChB,Synlogic President, Chief Executive Officer stated. I would like to thank the patients, clinicians and staff of our investigational sites who made this study possible. We look forward to further collaboration as we initiate our Phase 3 pivotal study, with the goal of bringing this potentially life-changing innovation in the treatment of PKU to patients.

Developing company Synlogichas confirmed these data supported the decision to continue with SYNB1934 as the drug candidate advancing to a phase 3 pivotal study which is expected to begin in the first half of 2023.

Read this article:
New Rare Disease Therapy Effectively Lowers Plasma Phe in Patients with PKU - MD Magazine

GSK plc (LSE/NYSE: GSK) and Tempus, a US-based precision medicine company, have entered into a three-year collaboration agreement that provides GSK with access to Tempus' AI-enabled platform, including its library of de-identified patient data. Through its leading Artificial Intelligence and Machine Learning (AI/ML) capability, GSK will work together with Tempus to improve clinical trial design, speed up enrolment and identify drug targets. This will contribute to GSK's R&D success rate and provide patients with more personalised treatment faster.

The new collaboration builds from the existing relationship between the companies that began in 2020 on clinical trial enrolment of patients with certain types of cancer. It will now expand GSK's access to de-identified patient data bringing greater scale and detail. Tempus' dataset draws from its work with over 40% of oncologists in the U.S. at academic medical centres and community hospitals.

Tony Wood, Chief Scientific Officer, GSK, said: "This collaboration will provide GSK with unique insights to discover better medicines and transform drug discovery. Tempus complements the work our team is already doing at the intersection of genomics and machine learning across both early discovery and clinical trials."

GSK's investments in human genetics, functional genomics and AI/ML have enabled the company to more than double the number of targets in the early portfolio since 2017 and have increased the proportion of those with genetic support beyond 70%. Medicines with genetic validation are twice as likely to become registered medicines. As a leader in AI-enabled precision medicine, Tempus has developed a platform that provides a rapid way of testing complex biomarker hypotheses. Powered by machine learning, this is an important component of selecting patients who could benefit from candidate medicines in GSK's portfolio in the future.

Eric Lefkofsky, Founder and CEO, Tempus, said: "GSK's data-first approach to therapeutic research aligns with our own, and we believe that Tempus has the resources and capabilities to complement GSK's dedication to data science, in a way others can't given the breadth and depth of our platform. We both share a commitment to providing patients with more personalised therapeutic options to help them live longer and healthier lives."

GSK and Tempus currently collaborate on an open label phase II study, which applies an innovative, data-driven approach designed to accelerate and streamline study timelines. This includes expediting the protocol development and intelligent site selection in under 60 days and enrolling its initial patients within three months of the study launch.

The expanded collaboration has a minimum financial commitment over three years, for which GSK made a $70 million initial payment. GSK then has an option to extend for two additional years.

About Tempus

Tempus is a technology company advancing precision medicine through the practical application of artificial intelligence in healthcare. With one of the world's largest libraries of clinical and molecular data, and an operating system to make that data accessible and useful, Tempus enables physicians to make real-time, data-driven decisions to deliver personalized patient care and in parallel facilitates discovery, development and delivery of optimal therapeutics. The goal is for each patient to benefit from the treatment of others who came before by providing physicians with tools that learn as the company gathers more data. For more information, visit tempus.com.

About GSK.ai

With more than 120 AI/ML experts, GSK's dedicated AI /ML team is the largest in-house strategic function in the biopharma industry and it is delivering a step-change in increasing R&D productivity, working closely with GSK's Research division. GSK teams are generating more data every quarter than in the company's entire history. At GSK, we believe AI has the potential to transform R&D because it enables our scientists to work better, faster and smarter so data helps us find the right medicine, using the right modality, for the right patient.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com/company

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK's Q2 Results for 2022 and any impacts of the COVID-19 pandemic.

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GSK : announces expanded collaboration with Tempus in precision medicine to accelerate R&D - Marketscreener.com

In 2022, Alain Aspect, John Clauser, and Anton Zeilinger were awarded the Nobel Prize for the first proof of quantum entanglement, a notion that Albert Einstein referred to as spooky action at a distance. This science first could massively impact the field of quantum computing, which uses quantum mechanics to solve problems that traditional computers cant handle.

Many scientific discoveries other than this one have or have had the capacity to change the course of history. Among other things, they have extended human life, harnessed energy, and provided an understanding of the evolution of the universe. (Read about some accidental discoveries that have changed the world.)

To assemble a list of discoveries that changed the course of history, 24/7 Tempo drew on a variety of scientific and general interest sources, including The Science Times, Famous Scientists, NASA, Discover Magazine, Smithsonian Magazine, Britannica, and PBS. This is not intended to be a comprehensive list, but a snapshot of discoveries or breakthroughs that we determined by editorial discretion, informed by the sources we consulted, to be of particular importance. We limited the number of discoveries concerning outer space because they have been covered in more detail in previous lists.

From revelations that influenced human health to technological advances to such universal basics as gravity and electricity, the discoveries on our list occurred across a variety of scientific fields. Some involved medicine and well-being, such as the discovery of penicillin. Others were biology-focused, while a number were made within the fields of physics and space. (These are the most important events in NASAs history.)

The 1800s saw nine key discoveries, among them the principles behind the battery and the electric generator. Another 11 occurred during the 20th century, including nuclear fission and continental drift.

Click here to see famous scientific discoveries that changed history forever

The scientific method encourages continual experimentation on existing theories, which sometimes disproves or alters our understanding of earlier results. For example, Albert Einsteins work on the theory of relativity challenged Isaac Newtons earlier understanding of physics.

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Famous Scientific Discoveries That Changed the Course of History - 24/7 Wall St.

Mysore/Mysuru: Karnataka State Construction Workers and Quarry Workers Association (AIUTUC) staged a protest on Monday against the Governments decision to release Rs. 433 crore from Karnataka State Building and Other Construction Workers Welfare Fund to Slum Clearance Board. They demanded its withdrawal and also urged to fulfill their other demands.

The protestors, who gathered in front of Deputy Commissioners Office, also demanded that Rs. 2 lakh be paid directly to the Bank Accounts of construction workers who have applied for subsidy to construct their houses, as per rules.

Alleging irregularities by the Labour Welfare Board in the procurement of food kit, booster kit and tools kit, provided during COVID-19 pandemic were of poor quality, they demanded a judicial probe into it. They also urged that the present Centre for Human Genetics (CHG) scheme be scrapped and instead, the registered construction workers and their families be provided with State Government Arogya Sanjeevani-2021 as a cashless service or Employees State Insurance (ESI) as a cashless facility. District General Secretary of the Association K.G. Somaraje Urs, District Secretary Mujahid Pasha, Vice-President Shivanna and others took part.

Excerpt from:
Construction workers seek fulfilment of their demands - Star of Mysore

DNA

Through news accounts and crime stories, were all familiar with the fact that the DNA in our cells reflects each individuals unique identity and how closely related we are to one another. The same is true for the relationships among organisms. DNA, or deoxyribonucleic acid, is the molecule that makes up an organisms genome in the nucleus of every cell. It consists of genes, which are the molecular codes for proteins the building blocks of our tissues and their functions. It also consists of the molecular codes that regulate the output of genes that is, the timing and degree of protein-making. DNA shapes how an organism grows up and the physiology of its blood, bone, and brains.

DNA is thus especially important in the study of evolution. The amount of difference in DNA is a test of the difference between one species and another and thus how closely or distantly related they are.

While the genetic difference between individual humans today is minuscule about 0.1%, on average study of the same aspects of the chimpanzee genome indicates a difference of about 1.2%. The bonobo (Pan paniscus), which is the close cousin of chimpanzees (Pan troglodytes), differs from humans to the same degree. The DNA difference with gorillas, another of the African apes, is about 1.6%. Most importantly, chimpanzees, bonobos, and humans all show this same amount of difference from gorillas. A difference of 3.1% distinguishes us and the African apes from the Asian great ape, the orangutan. How do the monkeys stack up? All of the great apes and humans differ from rhesus monkeys, for example, by about 7% in their DNA.

Geneticists have come up with a variety of ways of calculating the percentages, which give different impressions about how similar chimpanzees and humans are. The 1.2% chimp-human distinction, for example, involves a measurement of only substitutions in the base building blocks of those genes that chimpanzees and humans share. A comparison of the entire genome, however, indicates that segments of DNA have also been deleted, duplicated over and over, or inserted from one part of the genome into another. When these differences are counted, there is an additional 4 to 5% distinction between the human and chimpanzee genomes.

No matter how the calculation is done, the big point still holds: humans, chimpanzees, and bonobos are more closely related to one another than either is to gorillas or any other primate. From the perspective of this powerful test of biological kinship, humans are not only related to the great apes we are one. The DNA evidence leaves us with one of the greatest surprises in biology: the wall between human, on the one hand, and ape or animal, on the other, has been breached. The human evolutionary tree is embedded within the great apes.

The strong similarities between humans and the African great apes led Charles Darwin in 1871 to predict that Africa was the likely place where the human lineage branched off from other animals that is, the place where the common ancestor of chimpanzees, humans, and gorillas once lived. The DNA evidence shows an amazing confirmation of this daring prediction. The African great apes, including humans, have a closer kinship bond with one another than the African apes have with orangutans or other primates. Hardly ever has a scientific prediction so bold, so out there for its time, been upheld as the one made in 1871 that human evolution began in Africa.

The DNA evidence informs this conclusion, and the fossils do, too. Even though Europe and Asia were scoured for early human fossils long before Africa was even thought of, ongoing fossil discoveries confirm that the first 4 million years or so of human evolutionary history took place exclusively on the African continent. It is there that the search continues for fossils at or near the branching point of the chimpanzee and human lineages from our last common ancestor.

Due to billions of years of evolution, humans share genes with all living organisms. The percentage of genes or DNA that organisms share records their similarities. We share more genes with organisms that are more closely related to us.

Humans belong to the biological group known as Primates, and are classified with the great apes, one of the major groups of the primate evolutionary tree. Besides similarities in anatomy and behavior, our close biological kinship with other primate species is indicated by DNA evidence. It confirms that our closest living biological relatives are chimpanzees and bonobos, with whom we share many traits. But we did not evolve directly from any primates living today.

DNA also shows that our species and chimpanzees diverged from a common ancestor species that lived between 8 and 6 million years ago. The last common ancestor of monkeys and apes lived about 25 million years ago.

Continue reading here:
Genetics | The Smithsonian Institution's Human Origins Program

Science of genes, heredity, and variation in living organisms

Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms.[1][2][3]

Though heredity had been observed for millennia, Gregor Mendel, Moravian scientist and Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

Trait inheritance and molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded beyond inheritance to studying the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the cell, the organism (e.g. dominance), and within the context of a population. Genetics has given rise to a number of subfields, including molecular genetics, epigenetics and population genetics. Organisms studied within the broad field span the domains of life (archaea, bacteria, and eukarya).

Genetic processes work in combination with an organism's environment and experiences to influence development and behavior, often referred to as nature versus nurture. The intracellular or extracellular environment of a living cell or organism may switch gene transcription on or off. A classic example is two seeds of genetically identical corn, one placed in a temperate climate and one in an arid climate (lacking sufficient waterfall or rain). While the average height of the two corn stalks may be genetically determined to be equal, the one in the arid climate only grows to half the height of the one in the temperate climate due to lack of water and nutrients in its environment.

The word genetics stems from the ancient Greek genetikos meaning "genitive"/"generative", which in turn derives from genesis meaning "origin".[4][5][6]

The observation that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding.[7] [8] The modern science of genetics, seeking to understand this process, began with the work of the Augustinian friar Gregor Mendel in the mid-19th century.[9]

Prior to Mendel, Imre Festetics, a Hungarian noble, who lived in Kszeg before Mendel, was the first who used the word "genetic" in hereditarian context. He described several rules of biological inheritance in his works The genetic laws of the Nature (Die genetischen Gesetze der Natur, 1819).[10] His second law is the same as what Mendel published.[11] In his third law, he developed the basic principles of mutation (he can be considered a forerunner of Hugo de Vries).[12] Festetics argued that changes observed in the generation of farm animals, plants, and humans are the result of scientific laws.[13] Festetics empirically deduced that organisms inherit their characteristics, not acquire them. He recognized recessive traits and inherent variation by postulating that traits of past generations could reappear later, and organisms could produce progeny with different attributes.[14] These observations represent an important prelude to Mendels theory of particulate inheritance insofar as it features a transition of heredity from its status as myth to that of a scientific discipline, by providing a fundamental theoretical basis for genetics in the twentieth century.[10][15]

Other theories of inheritance preceded Mendel's work. A popular theory during the 19th century, and implied by Charles Darwin's 1859 On the Origin of Species, was blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents.[16] Mendel's work provided examples where traits were definitely not blended after hybridization, showing that traits are produced by combinations of distinct genes rather than a continuous blend. Blending of traits in the progeny is now explained by the action of multiple genes with quantitative effects. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrongthe experiences of individuals do not affect the genes they pass to their children.[17] Other theories included Darwin's pangenesis (which had both acquired and inherited aspects) and Francis Galton's reformulation of pangenesis as both particulate and inherited.[18]

Modern genetics started with Mendel's studies of the nature of inheritance in plants. In his paper "Versuche ber Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Naturforschender Verein (Society for Research in Nature) in Brnn, Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically.[19] Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.

The importance of Mendel's work did not gain wide understanding until 1900, after his death, when Hugo de Vries and other scientists rediscovered his research. William Bateson, a proponent of Mendel's work, coined the word genetics in 1905.[20][21] (The adjective genetic, derived from the Greek word genesis, "origin", predates the noun and was first used in a biological sense in 1860.)[22] Bateson both acted as a mentor and was aided significantly by the work of other scientists from Newnham College at Cambridge, specifically the work of Becky Saunders, Nora Darwin Barlow, and Muriel Wheldale Onslow.[23] Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London in 1906.[24]

After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1900, Nettie Stevens began studying the mealworm.[25] Over the next 11 years, she discovered that females only had the X chromosome and males had both X and Y chromosomes.[25] She was able to conclude that sex is a chromosomal factor and is determined by the male.[25] In 1911, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies.[26] In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.[27]

Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA, and scientists did not know which of the two is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation: dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, the AveryMacLeodMcCarty experiment identified DNA as the molecule responsible for transformation.[28] The role of the nucleus as the repository of genetic information in eukaryotes had been established by Hmmerling in 1943 in his work on the single celled alga Acetabularia.[29] The HersheyChase experiment in 1952 confirmed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.[30]

James Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA has a helical structure (i.e., shaped like a corkscrew).[31][32] Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what look like rungs on a twisted ladder.[33] The a-helix is a secondary structure and the twisting in the a-helix is caused by hydrogen bonds between the carboxyl (C=O) and the amine H (N-H) constituents of the polypeptide backbone.[34] This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for replication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand. This property is what gives DNA its semi-conservative nature where one strand of new DNA is from an original parent strand.[35]

Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process of protein production.[36] It was discovered that the cell uses DNA as a template to create matching messenger RNA, molecules with nucleotides very similar to DNA. The nucleotide sequence of a messenger RNA is used to create an amino acid sequence in protein; this translation between nucleotide sequences and amino acid sequences is known as the genetic code.[37]

With the newfound molecular understanding of inheritance came an explosion of research.[38] A notable theory arose from Tomoko Ohta in 1973 with her amendment to the neutral theory of molecular evolution through publishing the nearly neutral theory of molecular evolution. In this theory, Ohta stressed the importance of natural selection and the environment to the rate at which genetic evolution occurs.[39] One important development was chain-termination DNA sequencing in 1977 by Frederick Sanger. This technology allows scientists to read the nucleotide sequence of a DNA molecule.[40] In 1983, Kary Banks Mullis developed the polymerase chain reaction, providing a quick way to isolate and amplify a specific section of DNA from a mixture.[41] The efforts of the Human Genome Project, Department of Energy, NIH, and parallel private efforts by Celera Genomics led to the sequencing of the human genome in 2003.[42][43]

At its most fundamental level, inheritance in organisms occurs by passing discrete heritable units, called genes, from parents to offspring.[44] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants.[19][45] In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or whitebut never an intermediate between the two colors. These different, discrete versions of the same gene are called alleles.

In the case of the pea, which is a diploid species, each individual plant has two copies of each gene, one copy inherited from each parent.[46] Many species, including humans, have this pattern of inheritance. Diploid organisms with two copies of the same allele of a given gene are called homozygous at that gene locus, while organisms with two different alleles of a given gene are called heterozygous.

The set of alleles for a given organism is called its genotype, while the observable traits of the organism are called its phenotype. When organisms are heterozygous at a gene, often one allele is called dominant as its qualities dominate the phenotype of the organism, while the other allele is called recessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.[47]

When a pair of organisms reproduce sexually, their offspring randomly inherit one of the two alleles from each parent. These observations of discrete inheritance and the segregation of alleles are collectively known as Mendel's first law or the Law of Segregation. However, the probability of getting one gene over the other can change due to dominant, recessive, homozygous, or heterozygous genes. For example, Mendel found that if you cross homozygous dominate trait and homozygous recessive trait your odds of getting the dominant trait is 3:1. Real geneticist study and calculate probabilities by using theoretical probabilities, empirical probabilities, the product rule, the sum rule, and more.[48]

Geneticists use diagrams and symbols to describe inheritance. A gene is represented by one or a few letters. Often a "+" symbol is used to mark the usual, non-mutant allele for a gene.[49]

In fertilization and breeding experiments (and especially when discussing Mendel's laws) the parents are referred to as the "P" generation and the offspring as the "F1" (first filial) generation. When the F1 offspring mate with each other, the offspring are called the "F2" (second filial) generation. One of the common diagrams used to predict the result of cross-breeding is the Punnett square.

When studying human genetic diseases, geneticists often use pedigree charts to represent the inheritance of traits.[50] These charts map the inheritance of a trait in a family tree.

Organisms have thousands of genes, and in sexually reproducing organisms these genes generally assort independently of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendel's second law" or the "law of independent assortment," means that the alleles of different genes get shuffled between parents to form offspring with many different combinations. (Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.)

Often different genes can interact in a way that influences the same trait. In the Blue-eyed Mary (Omphalodes verna), for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have color at all or are white. When a plant has two copies of this white allele, its flowers are whiteregardless of whether the first gene has blue or magenta alleles. This interaction between genes is called epistasis, with the second gene epistatic to the first.[51]

Many traits are not discrete features (e.g. purple or white flowers) but are instead continuous features (e.g. human height and skin color). These complex traits are products of many genes.[52] The influence of these genes is mediated, to varying degrees, by the environment an organism has experienced. The degree to which an organism's genes contribute to a complex trait is called heritability.[53] Measurement of the heritability of a trait is relativein a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a trait with complex causes. It has a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition and health care, height has a heritability of only 62%.[54]

The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of deoxyribose (sugar molecule), a phosphate group, and a base (amine group). There are four types of bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The phosphates make hydrogen bonds with the sugars to make long phosphate-sugar backbones. Bases specifically pair together (T&A, C&G) between two backbones and make like rungs on a ladder. The bases, phosphates, and sugars together make a nucleotide that connects to make long chains of DNA.[55] Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.[56] These chains coil into a double a-helix structure and wrap around proteins called Histones which provide the structural support. DNA wrapped around these histones are called chromosomes.[57] Viruses sometimes use the similar molecule RNA instead of DNA as their genetic material.[58] Viruses cannot reproduce without a host and are unaffected by many genetic processes, so tend not to be considered living organisms.

DNA normally exists as a double-stranded molecule, coiled into the shape of a double helix. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA replication duplicates the genetic information by splitting the strands and using each strand as a template for synthesis of a new partner strand.[59]

Genes are arranged linearly along long chains of DNA base-pair sequences. In bacteria, each cell usually contains a single circular genophore, while eukaryotic organisms (such as plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length.[60] The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes, chromatin is usually composed of nucleosomes, segments of DNA wound around cores of histone proteins.[61] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome.

DNA is most often found in the nucleus of cells, but Ruth Sager helped in the discovery of nonchromosomal genes found outside of the nucleus.[62] In plants, these are often found in the chloroplasts and in other organisms, in the mitochondria.[62] These nonchromosomal genes can still be passed on by either partner in sexual reproduction and they control a variety of hereditary characteristics that replicate and remain active throughout generations.[62]

While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two of each chromosome and thus two copies of every gene.[46] The two alleles for a gene are located on identical loci of the two homologous chromosomes, each allele inherited from a different parent.

Many species have so-called sex chromosomes that determine the gender of each organism.[63] In humans and many other animals, the Y chromosome contains the gene that triggers the development of the specifically male characteristics. In evolution, this chromosome has lost most of its content and also most of its genes, while the X chromosome is similar to the other chromosomes and contains many genes. This being said, Mary Frances Lyon discovered that there is X-chromosome inactivation during reproduction to avoid passing on twice as many genes to the offspring.[64] Lyon's discovery led to the discovery of other things including X-linked diseases.[64] The X and Y chromosomes form a strongly heterogeneous pair.

When cells divide, their full genome is copied and each daughter cell inherits one copy. This process, called mitosis, is the simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, producing offspring that inherit their genome from a single parent. Offspring that are genetically identical to their parents are called clones.

Eukaryotic organisms often use sexual reproduction to generate offspring that contain a mixture of genetic material inherited from two different parents. The process of sexual reproduction alternates between forms that contain single copies of the genome (haploid) and double copies (diploid).[46] Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for most of their lifespan, with the haploid form reduced to single cell gametes such as sperm or eggs.

Although they do not use the haploid/diploid method of sexual reproduction, bacteria have many methods of acquiring new genetic information. Some bacteria can undergo conjugation, transferring a small circular piece of DNA to another bacterium.[65] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genomes, a phenomenon known as transformation.[66] These processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would be otherwise unrelated. Natural bacterial transformation occurs in many bacterial species, and can be regarded as a sexual process for transferring DNA from one cell to another cell (usually of the same species).[67] Transformation requires the action of numerous bacterial gene products, and its primary adaptive function appears to be repair of DNA damages in the recipient cell.[67]

The diploid nature of chromosomes allows for genes on different chromosomes to assort independently or be separated from their homologous pair during sexual reproduction wherein haploid gametes are formed. In this way new combinations of genes can occur in the offspring of a mating pair. Genes on the same chromosome would theoretically never recombine. However, they do, via the cellular process of chromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.[68] This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid cells. Meiotic recombination, particularly in microbial eukaryotes, appears to serve the adaptive function of repair of DNA damages.[67]

The first cytological demonstration of crossing over was performed by Harriet Creighton and Barbara McClintock in 1931. Their research and experiments on corn provided cytological evidence for the genetic theory that linked genes on paired chromosomes do in fact exchange places from one homolog to the other.[69]

The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between the points. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated.[70] For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage; alleles for the two genes tend to be inherited together. The amounts of linkage between a series of genes can be combined to form a linear linkage map that roughly describes the arrangement of the genes along the chromosome.[71]

Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell. Proteins are made up of one or more polypeptide chains, each of which is composed of a sequence of amino acids, and the DNA sequence of a gene (through an RNA intermediate) is used to produce a specific amino acid sequence. This process begins with the production of an RNA molecule with a sequence matching the gene's DNA sequence, a process called transcription.

This messenger RNA molecule then serves to produce a corresponding amino acid sequence through a process called translation. Each group of three nucleotides in the sequence, called a codon, corresponds either to one of the twenty possible amino acids in a protein or an instruction to end the amino acid sequence; this correspondence is called the genetic code.[72] The flow of information is unidirectional: information is transferred from nucleotide sequences into the amino acid sequence of proteins, but it never transfers from protein back into the sequence of DNAa phenomenon Francis Crick called the central dogma of molecular biology.[73]

The specific sequence of amino acids results in a unique three-dimensional structure for that protein, and the three-dimensional structures of proteins are related to their functions.[74][75] Some are simple structural molecules, like the fibers formed by the protein collagen. Proteins can bind to other proteins and simple molecules, sometimes acting as enzymes by facilitating chemical reactions within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the protein hemoglobin bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood.

A single nucleotide difference within DNA can cause a change in the amino acid sequence of a protein. Because protein structures are the result of their amino acid sequences, some changes can dramatically change the properties of a protein by destabilizing the structure or changing the surface of the protein in a way that changes its interaction with other proteins and molecules. For example, sickle-cell anemia is a human genetic disease that results from a single base difference within the coding region for the -globin section of hemoglobin, causing a single amino acid change that changes hemoglobin's physical properties.[76]Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of red blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly through blood vessels, having a tendency to clog or degrade, causing the medical problems associated with this disease.

Some DNA sequences are transcribed into RNA but are not translated into protein productssuch RNA molecules are called non-coding RNA. In some cases, these products fold into structures which are involved in critical cell functions (e.g. ribosomal RNA and transfer RNA). RNA can also have regulatory effects through hybridization interactions with other RNA molecules (such as microRNA).

Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotypes an organism displays. The phrase "nature and nurture" refers to this complementary relationship. The phenotype of an organism depends on the interaction of genes and the environment. An interesting example is the coat coloration of the Siamese cat. In this case, the body temperature of the cat plays the role of the environment. The cat's genes code for dark hair, thus the hair-producing cells in the cat make cellular proteins resulting in dark hair. But these dark hair-producing proteins are sensitive to temperature (i.e. have a mutation causing temperature-sensitivity) and denature in higher-temperature environments, failing to produce dark-hair pigment in areas where the cat has a higher body temperature. In a low-temperature environment, however, the protein's structure is stable and produces dark-hair pigment normally. The protein remains functional in areas of skin that are coldersuch as its legs, ears, tail, and faceso the cat has dark hair at its extremities.[77]

Environment plays a major role in effects of the human genetic disease phenylketonuria.[78] The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine, causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive intellectual disability and seizures. However, if someone with the phenylketonuria mutation follows a strict diet that avoids this amino acid, they remain normal and healthy.

A common method for determining how genes and environment ("nature and nurture") contribute to a phenotype involves studying identical and fraternal twins, or other siblings of multiple births.[79] Identical siblings are genetically the same since they come from the same zygote. Meanwhile, fraternal twins are as genetically different from one another as normal siblings. By comparing how often a certain disorder occurs in a pair of identical twins to how often it occurs in a pair of fraternal twins, scientists can determine whether that disorder is caused by genetic or postnatal environmental factors. One famous example involved the study of the Genain quadruplets, who were identical quadruplets all diagnosed with schizophrenia.[80]However, such tests cannot separate genetic factors from environmental factors affecting fetal development.

The genome of a given organism contains thousands of genes, but not all these genes need to be active at any given moment. A gene is expressed when it is being transcribed into mRNA and there exist many cellular methods of controlling the expression of genes such that proteins are produced only when needed by the cell. Transcription factors are regulatory proteins that bind to DNA, either promoting or inhibiting the transcription of a gene.[81] Within the genome of Escherichia coli bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acid tryptophan. However, when tryptophan is already available to the cell, these genes for tryptophan synthesis are no longer needed. The presence of tryptophan directly affects the activity of the genestryptophan molecules bind to the tryptophan repressor (a transcription factor), changing the repressor's structure such that the repressor binds to the genes. The tryptophan repressor blocks the transcription and expression of the genes, thereby creating negative feedback regulation of the tryptophan synthesis process.[82]

Differences in gene expression are especially clear within multicellular organisms, where cells all contain the same genome but have very different structures and behaviors due to the expression of different sets of genes. All the cells in a multicellular organism derive from a single cell, differentiating into variant cell types in response to external and intercellular signals and gradually establishing different patterns of gene expression to create different behaviors. As no single gene is responsible for the development of structures within multicellular organisms, these patterns arise from the complex interactions between many cells.

Within eukaryotes, there exist structural features of chromatin that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.[83] These features are called "epigenetic" because they exist "on top" of the DNA sequence and retain inheritance from one cell generation to the next. Because of epigenetic features, different cell types grown within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon of paramutation, have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.[84]

During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can affect the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low1 error in every 10100million basesdue to the "proofreading" ability of DNA polymerases.[85][86] Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure.[87] Chemical damage to DNA occurs naturally as well and cells use DNA repair mechanisms to repair mismatches and breaks. The repair does not, however, always restore the original sequence. A particularly important source of DNA damages appears to be reactive oxygen species[88] produced by cellular aerobic respiration, and these can lead to mutations.[89]

In organisms that use chromosomal crossover to exchange DNA and recombine genes, errors in alignment during meiosis can also cause mutations.[90] Errors in crossover are especially likely when similar sequences cause partner chromosomes to adopt a mistaken alignment; this makes some regions in genomes more prone to mutating in this way. These errors create large structural changes in DNA sequenceduplications, inversions, deletions of entire regionsor the accidental exchange of whole parts of sequences between different chromosomes (chromosomal translocation).

Mutations alter an organism's genotype and occasionally this causes different phenotypes to appear. Most mutations have little effect on an organism's phenotype, health, or reproductive fitness.[91] Mutations that do have an effect are usually detrimental, but occasionally some can be beneficial.[92] Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, about 70 percent of these mutations will be harmful with the remainder being either neutral or weakly beneficial.[93]

Population genetics studies the distribution of genetic differences within populations and how these distributions change over time.[94] Changes in the frequency of an allele in a population are mainly influenced by natural selection, where a given allele provides a selective or reproductive advantage to the organism,[95] as well as other factors such as mutation, genetic drift, genetic hitchhiking,[96] artificial selection and migration.[97]

Over many generations, the genomes of organisms can change significantly, resulting in evolution. In the process called adaptation, selection for beneficial mutations can cause a species to evolve into forms better able to survive in their environment.[98] New species are formed through the process of speciation, often caused by geographical separations that prevent populations from exchanging genes with each other.[99]

By comparing the homology between different species' genomes, it is possible to calculate the evolutionary distance between them and when they may have diverged. Genetic comparisons are generally considered a more accurate method of characterizing the relatedness between species than the comparison of phenotypic characteristics. The evolutionary distances between species can be used to form evolutionary trees; these trees represent the common descent and divergence of species over time, although they do not show the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria).[100]

Although geneticists originally studied inheritance in a wide range of organisms, researchers began to specialize in studying the genetics of a particular subset of organisms. The fact that significant research already existed for a given organism would encourage new researchers to choose it for further study, and so eventually a few model organisms became the basis for most genetics research.[101] Common research topics in model organism genetics include the study of gene regulation and the involvement of genes in development and cancer.

Organisms were chosen, in part, for convenienceshort generation times and easy genetic manipulation made some organisms popular genetics research tools. Widely used model organisms include the gut bacterium Escherichia coli, the plant Arabidopsis thaliana, baker's yeast (Saccharomyces cerevisiae), the nematode Caenorhabditis elegans, the common fruit fly (Drosophila melanogaster), the zebrafish (Danio rerio), and the common house mouse (Mus musculus).

Medical genetics seeks to understand how genetic variation relates to human health and disease.[102] When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and genetic pedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of Mendelian randomization to look for locations in the genome that are associated with diseases, a method especially useful for multigenic traits not clearly defined by a single gene.[103] Once a candidate gene is found, further research is often done on the corresponding (or homologous) genes of model organisms. In addition to studying genetic diseases, the increased availability of genotyping methods has led to the field of pharmacogenetics: the study of how genotype can affect drug responses.[104]

Individuals differ in their inherited tendency to develop cancer,[105] and cancer is a genetic disease.[106] The process of cancer development in the body is a combination of events. Mutations occasionally occur within cells in the body as they divide. Although these mutations will not be inherited by any offspring, they can affect the behavior of cells, sometimes causing them to grow and divide more frequently. There are biological mechanisms that attempt to stop this process; signals are given to inappropriately dividing cells that should trigger cell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process of natural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a cancerous tumor that grows and invades various tissues of the body.

Normally, a cell divides only in response to signals called growth factors and stops growing once in contact with surrounding cells and in response to growth-inhibitory signals. It usually then divides a limited number of times and dies, staying within the epithelium where it is unable to migrate to other organs. To become a cancer cell, a cell has to accumulate mutations in a number of genes (three to seven). A cancer cell can divide without growth factor and ignores inhibitory signals. Also, it is immortal and can grow indefinitely, even after it makes contact with neighboring cells. It may escape from the epithelium and ultimately from the primary tumor. Then, the escaped cell can cross the endothelium of a blood vessel and get transported by the bloodstream to colonize a new organ, forming deadly metastasis. Although there are some genetic predispositions in a small fraction of cancers, the major fraction is due to a set of new genetic mutations that originally appear and accumulate in one or a small number of cells that will divide to form the tumor and are not transmitted to the progeny (somatic mutations). The most frequent mutations are a loss of function of p53 protein, a tumor suppressor, or in the p53 pathway, and gain of function mutations in the Ras proteins, or in other oncogenes.

DNA can be manipulated in the laboratory. Restriction enzymes are commonly used enzymes that cut DNA at specific sequences, producing predictable fragments of DNA.[107] DNA fragments can be visualized through use of gel electrophoresis, which separates fragments according to their length.

The use of ligation enzymes allows DNA fragments to be connected. By binding ("ligating") fragments of DNA together from different sources, researchers can create recombinant DNA, the DNA often associated with genetically modified organisms. Recombinant DNA is commonly used in the context of plasmids: short circular DNA molecules with a few genes on them. In the process known as molecular cloning, researchers can amplify the DNA fragments by inserting plasmids into bacteria and then culturing them on plates of agar (to isolate clones of bacteria cells). "Cloning" can also refer to the various means of creating cloned ("clonal") organisms.

DNA can also be amplified using a procedure called the polymerase chain reaction (PCR).[108] By using specific short sequences of DNA, PCR can isolate and exponentially amplify a targeted region of DNA. Because it can amplify from extremely small amounts of DNA, PCR is also often used to detect the presence of specific DNA sequences.

DNA sequencing, one of the most fundamental technologies developed to study genetics, allows researchers to determine the sequence of nucleotides in DNA fragments. The technique of chain-termination sequencing, developed in 1977 by a team led by Frederick Sanger, is still routinely used to sequence DNA fragments.[109] Using this technology, researchers have been able to study the molecular sequences associated with many human diseases.

As sequencing has become less expensive, researchers have sequenced the genomes of many organisms using a process called genome assembly, which utilizes computational tools to stitch together sequences from many different fragments.[110] These technologies were used to sequence the human genome in the Human Genome Project completed in 2003.[42] New high-throughput sequencing technologies are dramatically lowering the cost of DNA sequencing, with many researchers hoping to bring the cost of resequencing a human genome down to a thousand dollars.[111]

Next-generation sequencing (or high-throughput sequencing) came about due to the ever-increasing demand for low-cost sequencing. These sequencing technologies allow the production of potentially millions of sequences concurrently.[112][113] The large amount of sequence data available has created the subfield of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data. A common problem to these fields of research is how to manage and share data that deals with human subject and personally identifiable information.

On 19 March 2015, a group of leading biologists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger, to edit the human genome in a way that can be inherited.[114][115][116][117] In April 2015, Chinese researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[118][119]

Originally posted here:
Genetics - Wikipedia

October 13, 2022

Scientists at the University of Oxford have carried out a study to investigate whether and how peoples genes influence how strong an immune response they mount after vaccination with either the Oxford-AstraZeneca or Pfizer-BioNTech COVID-19 vaccine.

The study has been published in Nature Medicine.

The scientists analysed DNA samples from 1,190 participants whod enrolled in the University of Oxfords COVID-19 vaccine clinical trials, as well as from 1,677 adults who had enrolled on the Com-COV research programme, and from children who had participated in clinical trials for the Oxford-AstraZeneca vaccine.

Journalists dialled in to this briefing to hear from the scientists who did the study discuss aspects such as:

which genes in people determine how well their immune system responds to Covid vaccination?

which bits of the immune system seem to respond differently with different versions of these genes?

are there certain populations that tend to have specific versions of these genes?

what is the normal role of these genes?

are there implications?

Speakers included:

Prof Julian Knight, Professor of Genomic Medicine, Wellcome Centre for Human Genetics, University of Oxford

Dr Alexander Mentzer, Group Leader at the Wellcome Centre for Human Genetics, University of Oxford, and an Infectious Disease doctor

Dr Daniel OConnor, University Research Lecturer and Senior Bioinformatician, Oxford Vaccine Group, University of Oxford

This Briefing was accompanied by an SMC Roundup of comments.

Original post:
Study looking at human genetics and Covid vaccine immune responses - Science Media Centre

Note: All in-person attendees and media must be fully vaccinated. Prior to arriving on-site, please upload your vaccination record to the ASHG/Safe Expo Portal to ensure timely access to the event.

ROCKVILLE, MD--Thousands of human genomics and genetics researchers, clinicians, counselors, public health experts and others will attend the annual meeting of the American Society of Human Genetics (ASHG) in Los Angeles, California, October 25-29. Journalists covering ASHG 2022, the world's largest and most influential human genetics and genomics meeting, will have access to thousands of scientific papers and oral presentations, workshops, and collaborative events. The annual meeting fosters discussion about individual research and the big picture of cutting-edge science across the field. It is a remarkable opportunity to meet sources, chart trends and uncover story ideas.

This years meeting will offer in-person opportunities for networking, sharing the latest scientific findings with nearly 400 live presentations, more than 2,500 published posters, and over 200 exhibitors. A post-meeting virtual program will capture highlights, provide additional learning, and feature live networking for those unable to attend in person.

ASHG is thrilled to bring together attendees in person for the first time in three years to present, learn and discuss the most recent findings in human genetics and genomics in the worlds largest venue for geneticists on earth, said ASHG President Charles Rotimi, PhD. The breadth of science being presented at this years meeting reflects the expansive reach of genomics in all areas of research and its role to help promote health and prevent disease.

This years program features exciting sessions highlighting many breakthroughs in research progress and ongoing field dialogue on emerging issues that can realize benefits of this research for science, health, and society. Learn more in the online planner.

COVID-19 in the Post-Pandemic Era: Long COVID, Vaccine Response, and Beyond This event will share information about the contributions of human genetic variation to susceptibility to COVID and risk of long COVID as well as response to vaccines.

Tuesday, October 25, from 4:30 p.m. 6:00 p.m.

Presidential Symposium on H3Africa and the African Genomics Ecosystem This event featuring former NIH Director, Francis Collins, MD will highlight Africa, a profoundly dynamic and diverse continent, and its major advances, new directions and goals, emerging scientific leadership, exciting investment in technology infrastructure, and more. How can and will genomics in Africa spread its wings and what areas are most exciting?Thursday, October 27, 8:30 a.m.10:00 a.m.

Upset the Set Up: Moving from Community Engagement to Community Empowerment The overarching objectives of this session are to: (1) examine ongoing efforts that break the mold of transactional community engaged research; and (2) explore remaining needs for community empowered research in genetics and genomics. It does so by bringing together diverse stakeholders in the field to consider the need to transition from community engagement to community empowerment.

Friday, October 28, from 8:30 a.m.- 10:00 a.m.

Research presented at the annual meeting will also cover:

In addition, ASHG will hold a special media availability session with geneticists from ASHGs Public Education and Awareness Committee on Wednesday, October 26 from 9:45-10:15 a.m., exclusively for registered media. During this discussion, presenters will highlight new initiatives; findings related to basic, translational, and clinical genetics; therapeutics and drug discovery; population genetics and evolution; and more. Media can register for credentials here.

* * *

About the American Society of Human Genetics (ASHG)

Founded in 1948, the American Society of Human Genetics is the primary professional membership organization for human genetics specialists worldwide. Its community of nearly 8,000 members include researchers, academicians, clinicians, laboratory practice professionals, genetic counselors, nurses, and others with an interest in human genetics. The Society serves scientists, health professionals, and the public by providing forums to: (1) share research results through theASHG Annual Meetingand inThe American Journal of Human GeneticsandHuman Genetics and Genomics Advances; (2) advance genetic research by advocating for research support; (3) educate current and future genetics professionals, health care providers, advocates, policymakers, educators, students, and the public about all aspects of human genetics; and (4) promote genetic services and support responsible social and scientific policies. For more information, visit:http://www.ashg.org.

6120 Executive Blvd, Suite 500 | Rockville, MD 20852 | 301.634.7300 |society@ashg.org|www.ashg.orgConnect with ASHG onTwitter(@GeneticsSociety) |Facebook|LinkedIn

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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ASHG 2022 in Los Angeles brings together researchers from around the world to advance discoveries in genetics, genomics research - EurekAlert

Eric Green, M.D., Ph.D., Promoted to Chief Scientific Officer

SOUTH SAN FRANCISCO, Calif., October 13, 2022--(BUSINESS WIRE)--Maze Therapeutics, a company translating genetic insights into new precision medicines, today announced that Harold Bernstein, M.D., Ph.D., a 30-year industry veteran, has been appointed as president, head of research and development (R&D) and chief medical officer. In addition, Eric Green, M.D., Ph.D., who has served as Mazes senior vice president, research and translational sciences, has been promoted to chief scientific officer.

"Harold brings an impressive combination of industry and academic experience, as well as the unique perspective of a practicing physician, to the Maze team at an important stage of our development. Further, with much of Harolds experience having focused on human genetics, he is a natural candidate for this position, and Im thrilled to welcome him to our team and mission," said Jason Coloma, Ph.D., chief executive officer of Maze. "I am also pleased to announce the promotion of Eric to CSO, who has been a true leader and driving force behind much of Mazes platform and pipeline advancement since our founding. Eric and Harold will be instrumental in executing the advancement of our diverse pipeline, which spans monogenic diseases like Pompe disease, and more complex diseases, like chronic kidney disease. I look forward to partnering with these two experts as we deliver on our vision of harnessing the power of human genetics to transform the lives of patients."

"Maze has attracted some of the best minds in biotech and has proven itself through impressive progress since its founding, including the build-out of its Compass platform and rapid advancement into the clinic," said Dr. Bernstein. "I was drawn to the Maze teams lofty goal of shifting the paradigm in medicine, in particular for more complex diseases such as chronic kidney disease, during an unprecedented time for the field of genetics and precision medicine. As head of R&D, I look forward to shaping and contributing to a creative strategy and thorough scientific process aimed at delivering new, genetic-based medicines. I am thrilled to join the Maze team as we urgently work to create and advance therapeutically meaningful treatments to help patients in need."

Story continues

Dr. Bernstein brings more than three decades of experience in basic scientific research, translational medicine and clinical development both in industry and academia. He joins Maze from BioMarin, where he served as senior vice president, chief medical officer and head of global clinical development. In this role, he was responsible for fortifying clinical development from early to late stages, working seamlessly with research discovery and overseeing the late-stage and lifecycle products. Prior to BioMarin, he was head of translational medicine and vice president of global medicines development and medical affairs at Vertex, and earlier held roles at Merck, including head of early development for cardiometabolic diseases. Dr. Bernstein was professor of pediatrics and a senior investigator at the Cardiovascular Research Institute and the Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco (UCSF). He also served as attending physician at UCSF Benioff Childrens Hospital in pediatric cardiology, and at the Mount Sinai Kravis Childrens Hospital in cardiovascular genetics. Dr. Bernstein currently holds an appointment as adjunct professor of pediatrics and the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai. He studied biomedical science, human genetics and medicine at the Mount Sinai School of Medicine, earning an M.Phil., Ph.D. and M.D. He completed a pediatric residency, cardiology fellowship and postdoctoral fellowship at UCSF and earned an A.B. in biological sciences from Harvard College.

Dr. Green is a physician-scientist and entrepreneur with more than 15 years of experience building and operating innovative scientific organizations. Prior to Maze, Dr. Green was an entrepreneur-in-residence at Third Rock Ventures, where he was involved in launching and building multiple Third Rock portfolio companies, including MyoKardia where he led the translational research group working on mavacamten, which was eventually acquired by Bristol Myers Squibb. Dr. Green is a board-certified physician with training in internal medicine and cardiovascular medicine from Brigham and Womens Hospital. He holds an M.D. and Ph.D. in chemical and systems biology from Stanford University and an A.B. in history and science from Harvard College.

About Maze Therapeutics

Maze Therapeutics is a biopharmaceutical company applying advanced data science methods in tandem with a robust suite of research and development capabilities to advance a pipeline of novel precision medicines for patients with genetically defined diseases. Maze has developed the Maze CompassTM platform, a proprietary, purpose-built platform that combines human genetic data, functional genomic tools and data science technology to map novel connections between known genes and their influence on susceptibility, timing of onset and rate of disease progression. Using Compass, Maze is building a broad portfolio of wholly owned and partnered programs. Maze is based in South San Francisco. For more information, please visit mazetx.com, or follow us on LinkedIn and Twitter.

View source version on businesswire.com: https://www.businesswire.com/news/home/20221013005211/en/

Contacts

Jillian Connell, Maze Therapeuticsjconnell@mazetx.com 650.850.5080

Media: Katie Engleman, 1ABkatie@1abmedia.com

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Maze Therapeutics Appoints Harold Bernstein, M.D., Ph.D., as President, Research and Development and Chief Medical Officer - Yahoo Finance

Pan has several meanings.

As a noun, it refers to a round metal container that often has a long handle and a lid.

As a verb, it means criticism, like panning a film.

Peter Pan refers to an adult who doesnt want to behave like one, from Sir James Barries play about the boy who didnt want to grow up

As a prefix, pan, from the Greek, means all, every, whole, and all-inclusive.

Sigmund Freud reportedly used the term pan-sexualism in 1914, to mean sex as a motivator of all things.

In genetics, the human pangenome is a complete reference of human genome diversity. It is envisioned as a new type of map that represents all of the ways that the sequence of 3,054,832 billion DNA base pairs the building blocks of a genome vary, plus or minus a few from short repeated sequences. The depiction is so densely packed that it resembles a map of the New York City subway system.

The Human Pangenome Reference Consortium is spearheading creation of a genome reference representation that can capture all human genome variation and support research on the full diversity of populations.

Such a resource is of course long overdue. Now that more than 30 million people have had their genomes sequenced, its strange to think back about talk of the human genome, as if we are all identical identical for each of the 4 DNA nitrogenous bases A, C, T, or G occupying each of the 3 billion slots. Were not clones. But most biotechnologies take about 3 decades to mature, and since the human genome project got started in the early 1990s, things seem right about on schedule for a broader look.

Back in the mid 1980s, when I first attended meetings where the idea of sequencing the human genome surfaced, the task was expected to take at least a decade. About 93 percent of the first draft human genome sequence published in 2001 from the NHGRI and partners came from only 11 people, with 70 percent of the total from just one man, who was of 37 percent African ancestry and 57 percent European ancestry. The human genome published from Celera Genomics was reportedly Craig Venters, head of that company.

After that, genome sequences began to trickle in, from celebrities, other rich folks, a handful of journalists who cranked out articles and books revealing their genetic selves, and a series of firsts African, Han Chinese, and several modern peoples with ancient roots.

Its a little mind boggling to realize that today we can access our genome sequence data on our smartphones.

Researchers began to catalog human genome diversity as the human genome project was winding down, by identifying single-base places in genomes that vary among individuals. These are the single nucleotide polymorphisms, or SNPs. As SNP collections peppered the chromosomes ever more densely, researchers quickly realized that new tools were needed to depict the unfurling diversity of our DNA.

Despite these sequencing advances, we still have a lot to learn about human genetic diversity, and that calls for comparisons. Enter the human pangenome effort.

The diversity of our genome sequences is staggering. A study of whole genome sequences for 53,831 people found distinctions at 400 million places! Most were SNPs or an extra or missing DNA base. But it may be that much of our variability comes from only a few people. About 97 percent of the 400 million points of distinction came from less than one percent of the 53,831 participants, with 46 percent of them in only one person. We vary genetically in many ways, and some of us vary more than others, but we are all human.

For a few years, researchers compiled reference genome sequences to account for diversity in specific populations. These digital sequences displayed the most common DNA base found in many genomes from the group, at each point. But updating reference genomes took a long time, and it was a thankless task, never complete. By 2010, when more data from Asians and Africans had been added to reference genomes, still 5 million gaps in the reference sequences remained.

As the data swiftly outgrew attempts to capture genome diversity in a simple, clear visual tool, the idea emerged of the human pangenome: a complete reference of human genome diversity. The Human Pangenome Project officially began in 2019, and within a year, filled in the gaps remaining in genome sequences. The goal was to display the genome sequences of an initial 350 people from diverse ethnic groups, using computational pangenomics tools to create visuals called genome graphs.

In a genome graph, color-coded bases superimposed on the DNA depiction indicate how people vary, site-by-site. Like a geographical map with symbols denoting campgrounds, rest stops, and places of interest, genome graphs indicate SNPs and also missing parts of the genome sequence, extra hunks, and inverted regions. It also indicates meanings and context, such as distinguishing protein-encoding genes from control sequences, and highlighting places where the DNA sequence can be read from different starting points, which tells the cell to make different protein products.

The data pouring into the human pangenome project are coming from population biobanks and various genome sequencing projects. When all of this information is superimposed on the chromosome-length sketches, the genome graph indeed begins to resemble a subway map.

I grew up riding the New York City subways. Just as more train lines converge at the citys center, Manhattan, with only a few lines extending into the boroughs, so too are the protein-encoding genes clustered toward each chromosomes centromere, growing more sparse out towards the tips, the telomeres.

I think back in wonder at the first human genome meeting I attended, in 1986, I think in Boston. Its been a long, strange trip, but were finally beginning to understand how a 4-letter language can spell out the astounding diversity of the human animal.

Originally posted here:
The Age of the Pangenome Dawns - DNA Science - PLOS