Category Archives: Human Genetics

Type 2 diabetes genetic mapping identifies new 'loci' Science Daily Scientists are closer to understanding the genetic causes of type 2 diabetes by identifying 111 new chromosome locations ('loci') on the human genome that indicate susceptibility to the disease, according to a UCL-led study in collaboration with ...

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Type 2 diabetes genetic mapping identifies new 'loci' - Science Daily

Scientist discovers why skin peels off Afrikaners' hands and feet

Dave Chambers | 2017-05-11 10:49:45.0

Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema, or 'Oudtshoorn skin', in South Africa's Afrikaner population. Image by: Professor Michele Ramsay

Thandiswa Ngcungcu is the scientist responsible for the final breakthrough. She chose keratolytic winter erythema as a topic for her doctoral studies.

The disease colloquially known as Oudtshoorn skin causes redness on the palms and soles with cycles in which thick sections of skin peel especially during winter.

Wits researchers started studying the disorder in the late 1980s and in 1997 the trait was mapped to the short arm of chromosome 8.

But the mutation remained elusive until Ngcungcu decided to try to track it down said Wits spokeswoman Lisa Rautenbach.

Writing in this months edition of the American Journal of Human Genetics Ngcungcu and her fellow researchers say they discovered a mutation in a region between genes which was present in all Oudtshoorn skin sufferers they studied.

At the same time a researcher from the University of Bergen discovered the cause of the disease in Norwegians. When they compared notes they found an overlap in a critical genomic region called an enhancer.

After another years work said Rautenbach they demonstrated that the mutation causes a nearby gene to produce more protein than normal the likely cause of skin peeling.

Solving the mystery of (Oudtshoorn skin) was a journey of data analysis ancestry mapping genomic comparison and global collaboration said Rautenbach.

The discovery will allow dermatologists to make a definitive diagnosis of the disease in patients and is a starting point for researching possible treatments.

Rautenbach said Afrikaners are at high risk of inheriting several genetic disorders the best known being familial hypercholesterolaemia inherited high cholesterol leading to heart attacks early in life and porphyria sensitivity of the skin to ultra-violet exposure and adverse reactions to specific drugs.

These disorders are common because of founder mutations brought to South Africa by small groups of immigrants who settled in the Cape of Good Hope and whose descendants are now spread throughout the country she said.

Oudtshoorn skin was first described in 1977 by Wits dermatologist George Findlay. He noticed that it occurred in families and that if a parent has it about half the children inherit it in every generation.

Ngcungcu is now examining the genetics of another skin disorder albinism and will lecture in human genetics at Wits from July.

-TMG Digital/TimesLIVE

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Scientist discovers why skin peels off Afrikaners' hands and feet - Times LIVE

May 11, 2017 A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

When a group of researchers in the Undiagnosed Disease Network at Baylor College of Medicine realized they were spending days combing through databases searching for information regarding gene variants, they decided to do something about it. By creating MARRVEL (Model organism Aggregated Resources for Rare Variant ExpLoration) they are now able to help not only their own lab but also researchers everywhere search databases all at once and in a matter of minutes.

This collaborative effort among Baylor, the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and Harvard Medical School is described in the latest online edition of the American Journal of Human Genetics.

Big data search engine

"One big problem we have is that tens of thousands of human genome variants and phenotypes are spread throughout a number of databases, each one with their own organization and nomenclature that aren't easily accessible," said Julia Wang, an M.D./Ph.D. candidate in the Medical Scientist Training Program at Baylor and a McNair Student Scholar in the Bellen lab, as well as first author on the publication. "MARRVEL is a way to assess the large volume of data, providing a concise summary of the most relevant information in a rapid user-friendly format."

MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER, all separate databases to which researchers across the globe have contributed, sharing tens of thousands of human genome variants and phenotypes. Since there is not a set standard for recording this type of information, each one has a different approach and searching each database can yield results organized in different ways. Similarly, decades of research in various model organisms, from mouse to yeast, are also stored in their own individual databases with different sets of standards.

Dr. Zhandong Liu, assistant professor in pediatrics - neurology at Baylor, a member of the Jan and Dan Duncan Neurological Research Institute at Texas Children's and co-corresponding author on the publication, explains that MARRVEL acts similar to an internet search engine.

"This program helps to collate the information in a common language, drawing parallels and putting it together on one single page. Our program curates model organism specific databases to concurrently display a concise summary of the data," Liu said.

Supporting researchers

A user can first search for a gene or variant, Wang explains. Results may include what is known about this gene overall, whether or not that gene is associated with a disease, whether it is highly occurring in the general population and how it is affected by certain mutations.

"MARRVEL helps to facilitate analysis of human genes and variants by cross-disciplinary integration of 18 million records so we can speed up the discovery process through computation," Liu said. "All this information is basically inaccessible unless researchers can access it efficiently and apply it to their own work to find causes, treatments and hopefully identify new diseases."

Collaboration

This project started as a necessity for the Model Organism Screening Center for the Undiagnosed Disease Network at Baylor, but as it grew, the group began reaching out to researchers in different disciplines for feedback on how MARRVEL might benefit them.

"This program is just the start. I think our tool is going to be a model for us to help clinicians and basic scientists more efficiently use the information already publicly available," Wang said. "It will help us understand and process all of the different mutations that researchers are discovering."

"The most exciting part is how this project is bringing so many different researchers together," Liu said. "We are working with labs we might not have normally collaborated with, trying to put together a puzzle of all this data."

Both Wang and Liu are thankful to the contributions from the genetics communities allowing them access to the databases as they developed MARRVEL.

Others who contributed to the findings include Drs. Rami Al-Ouran, Seon-Young Kim, Ying-Wooi Wan, Michael Wangler, Shinya Yamamoto, Hsiao-Tuan Chao, and Hugo Bellen (Howard Hughes Medical Institute at Baylor) all with Baylor College of Medicine; Yanhui Hu, Aram Comjean, Stephanie E. Mohr, and Norbert Perrimon (Howard Hughes Medical Institute at Harvard Medical School) all with Harvard Medical School.

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A team of scientists from a number of institutions around the world, including Baylor College of Medicine, has discovered that rare neurological syndromes for which there was no cause can be the result of variations in the ...

An international team of scientists has discovered that the gene, OGDHL, a key protein required for normal function of the mitochondriathe energy-producing factory of the celland its chaperone, nardilysin (NRD1) are ...

An algorithm developed by Saudi Arabia's King Abdullah University of Science and Technology (KAUST) scientists has the potential to help patients with mysterious ailments find genetic causes for their undiagnosed diseases.

An international team of researchers from institutions around the world, including Baylor College of Medicine, has discovered that mutations of the OTUD6B gene result in a spectrum of physical and intellectual deficits. This ...

In a study published today in PLoS ONE, a team of researchers reports solving a medical mystery in a day's work. In record-time detective work, the scientists narrowed down the genetic cause of intellectual disability in ...

When a group of researchers in the Undiagnosed Disease Network at Baylor College of Medicine realized they were spending days combing through databases searching for information regarding gene variants, they decided to do ...

A new Northwestern Medicine study, published in Genes and Development, has identified two DNA elements crucial to the activation of a set of genes that drive the early development of embryos, and which also play an important ...

Reported in Nature today, one of the largest sets of high quality human induced pluripotent stem cell lines from healthy individuals has been produced by a consortium involving the Wellcome Trust Sanger Institute. Comprehensively ...

Over the last decade, it has made good sense to study the genetic drivers of cancer by sequencing a tiny portion of the human genome called the exome - the 2% of our three billion base pairs that "spell out" the 21,000 genes ...

Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or 'Oudtshoorn skin', in Afrikaners.

Men and women differ in obvious and less obvious waysfor example, in the prevalence of certain diseases or reactions to drugs. How are these connected to one's sex? Weizmann Institute of Science researchers recently uncovered ...

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Compiling big data in a human-centric way - Medical Xpress

Science has long proven that genetics and DNA abnormalities can elevate the risk of contracting diseases like cystic fibrosis and hemophilia. While researchers also have believed that genes can influence the risk of coronary heart disease, a new study says a patients lifestyle can have a greater impact than hereditary background.

Research by The Center for Human Genetic Research at Massachusetts General Hospital in Boston found that while genetics can double the risk of heart disease, a healthy lifestyle can cut that risk back in half. Medical researchers analyzed records from more than 55,000 patients and discovered the risk of heart disease is not merely a function of genetics or lifestyle, but a complex mix of both.

Investigators examined the data and created a genetic score based on 50 genes associated with heart disease. They then developed a lifestyle score influenced by factors like smoking status, diet, weight and level of fitness. The findings revealed that while a person with high genetic risk and a bad lifestyle had an 11 percent chance of having a coronary event in the next 10 years, those who also lived a healthy lifestyle cut that risk to only 5 percent.

For heart attack at least, DNA is not destiny, says Dr. Sekar Kathiresan, senior researcher. You have control over your risk for heart attack, even if youve been dealt a bad hand.

Researchers also found those with a low genetic risk (3 percent or less) nearly doubled their overall risk to 5.8 percent when they lived an unhealthy lifestyle. While doctors often have used genetic testing and risk profiles to better inform patients, that information sometimes can lull at-risk patients into thinking theres nothing they can do to overcome their genetics. For some patients, that can reduce the incentive to exercise, improve diet and live a healthier lifestyle. Researchers now say that even for a patient with a long history of heart attacks in their family, living a healthy lifestyle can significantly decrease their risk of coronary heart disease.

The research confirms the findings of four other studies that indicate lifestyle choices can positively or negatively influence genetic risk. It gives hope to patients with an elevated risk of heart disease and offers scientific evidence that they can actively reduce their risk of a cardiac event.

According to the American Heart Association, age, gender and heredity are the major unchangeable factors that can impact the risk of heart and blood vessel disease. A persons risk generally rises as they grow older, and men have a greater risks than women. Yet the AHA notes that despite any CHD risk factors, a healthy lifestyle can always improve the prospects.

According to the AHA website, Just as you cant control your age, sex and race, you cant control your family history. Therefore, its even more important to treat and control any other risk factors you have.

The National Heart, Lung and Blood Institute said patients can control many CHD risk factors with healthy lifestyle changes that positively impact blood cholesterol, high blood pressure, weight and obesity. These heart-healthy lifestyle changes includes diets that call for vegetables, fruits, whole grains and lean meats while limiting sodium, saturated fats, added sugars and alcohol. Patients also can engage in more exercise and physical activity to reduce weight and aim for a body mass index that is below 25. The American Heart Association recommends roughly 30 minutes of exercise five days per week.

Even things like stress and depression have been proven to play a role in CHD. When lifestyle changes arent enough, patients also can use medications like beta-blockers and statins to reduce things that could lead to a heart attack. The National Institutes of Health says even more than genes, family eating and exercise habits can influence the next generation.

Making lifestyle changes can be hard. But if you make these changes as a family, it may be easier for everyone to prevent or control their CHD risk factors, according to the NIH website.

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Bad genes? Get a healthier lifestyle - Quad-Cities Online

Self Regional Hall, a new 17,000-square-foot, state-of-the art facility that will house the Clemson University Center for Human Genetics, has opened on the campus of the Greenwood Genetic Center.

The facility will enable Clemsons growing genetics program to collaborate closely with the long tradition of clinical and research excellence at theGreenwood Genetic Center, combining basic science and clinical care. The center will initially focus on discovering and developing early diagnostic tools and therapies for autism, cognitive developmental disorders, oncology and lysosomal disorders. The building will house eight laboratories and several classrooms, conference rooms and offices for graduate students and faculty.

According to theCenters for Disease Control and Prevention, one in six children between the ages of 3 and 17, roughly 15 percent, suffers from some type of developmental disorder.

Opening Self Regional Hall means that we will be able to do even more to help children with genetic disorders, and their families, and to educate graduate students who will go out into the world and make their own impact, said President James P. Clements.

As the parent of a child with special needs, the kind of research that you are doing here is especially meaningful and important to me and my family, Clements said during the event. As you all know, an early diagnosis can make a huge difference for a child and their family because the earlier you can figure out what a child needs, the earlier you can intervene and begin treatment.

Self Regional Hall is a state-of-the-art facility that provides the resources our scientists need to understand the genetic underpinnings of disorders, said Mark Leising, interim dean of theCollege of Scienceat Clemson. This facility, and its proximity to the Greenwood Genetic Center, elevates our ability to attract the brightest scientific talent to South Carolina and enhances our efforts to tackle genetic disorders.

The facilitys name recognizes the ongoing support fromSelf Regional Healthcare, a health care system in Upstate South Carolina that has grown from the philanthropy of the late James P. Self, a textile magnate who founded Self Memorial Hospital in 1951.

Self Regional Healthcares vision is to provide superior care, experience and value. This vision includes affording our patients with access to cutting-edge technology and the latest in health care innovation and genomic medicine, without a doubt, is the future of health care, said Jim Pfeiffer, president and CEO of Self Regional Healthcare. The research and discoveries that will originate from this center will provide new options for those individuals facing intellectual and developmental disabilities, and will provide our organization with innovative capabilities and treatment options for our patients.

We are pleased to welcome Clemson University to Greenwood as the first academic partner on our Partnership Campus, added Dr. Steve Skinner, director of the Greenwood Genetic Center. This is the next great step in a collaboration that has been developing over the past 20-plus years. We look forward to our joint efforts with both Clemson and Self Regional Healthcare to advance the research and discoveries that will increase our understanding and treatment of human genetic disorders.

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Clemson World Magazine | Clemson Center for Human Genetics ... - Clemson World magazine

Genetics of childhood 'overgrowth' unraveled Science Daily They also showed that many of the overgrowth genes are also involved in driving cancer growth, though intriguingly, the types of mutations involved in promoting human growth and cancer growth are often different. The researchers collected samples and ...

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Genetics of childhood 'overgrowth' unraveled - Science Daily

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Scientists find genetic mutation responsible for rare skin disease in Afrikaners Science Daily Researchers at the Sydney Brenner Institute for Molecular Bioscience and the Division of Human Genetics at Wits, in collaboration with peers in Europe, the US and Canada published this research in the May issue of the American Journal of Human Genetics.

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Scientists find genetic mutation responsible for rare skin disease in Afrikaners - Science Daily

May 5, 2017 Credit: Wits University

Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or 'Oudtshoorn skin', in Afrikaners.

Researchers at the Sydney Brenner Institute for Molecular Bioscience and the Division of Human Genetics at Wits, in collaboration with peers in Europe, the US and Canada published this research in the May issue of the American Journal of Human Genetics.

KWE causes a redness of the palms and soles with consecutive cycles of peeling of large sections of thick skin, often exacerbated during winter months. Oudtshoorn is a town in the Western Cape province of South Africa where the disorder was present in large families.

Afrikaners are Afrikaans-language speakers descended from predominantly Dutch, German and French settlers, who arrived in South Africa in the 17th and 18th centuries. Afrikaners have a high risk for several genetic disorders, the best known being familial hypercholesterolaemia (inherited high cholesterol leading to heart attacks early in life) and porphyria (sensitivity of the skin to ultra-violet exposure and adverse reactions to specific drugs).

These disorders are common because of founder mutations brought to South Africa by small groups of immigrants who settled in the Cape of Good Hope and whose descendants are now spread throughout the country. KWE is one of these less well-known founder genetic disorders.

KWE was first described as a unique and discrete skin disorder in 1977 by Wits dermatologist, Professor George Findlay. He noticed that it occurred in families and had a dominant mode of inheritance i.e., on average, if a parent has the condition about half the children inherit it in every generation.

In addition to identifying the genetic mutation for scientific purposes, this research now enables dermatologists to make a definitive diagnosis of KWE in patients. It further enables researchers to understand similar skin disorders and is a starting point for developing possible treatments.

Gene mutations

Since the late 1980s, three MSc and three PhD students at Wits researched the disorder, firstly under the supervision of Professor Trefor Jenkins and from about 1990 guided by Professor Michle Ramsay, Director and Research Chair in the Sydney Brenner Institute for Molecular Bioscience. In 1997, Wits MSc student Michelle Starfield and a group in German mapped the KWE trait to a region on the short arm of chromosome 8. The researchers showed that it was likely that the South African families all had the same mutation, but that the German family had a different mutation.

In 1997, Wits MSc student Michelle Starfield and a group in Germany mapped the KWE trait to a region on the short arm of chromosome 8. The researchers showed that it was likely that the South African families all had the same mutation but that the German family had a different mutation. This research preceded the sequencing of the human genome and subsequent research focused on characterising this region of the genome and examining good candidate genes. The KWE mutation remained elusive.

In 2012 Thandiswa Ngcungcu, then a Wits MSc student in Human Genetics whom Ramsay supervised, chose KWE as a topic for her PhD. Ngcungu's research involved large-scale DNA sequencing during an internship on the Next Generation Scientist Programme in Novartis, Basel. The mutation was not detected by conventional data analysis so copy number variants (genetic changes) where regions of the genome are duplicated or deleted were investigated. Ngcungcu and the researchers then discovered a mutation in a region between genes that was present in all South African KWE-affected individuals studied.

During this time Dr Torunn Fiskerstrand, University of Bergen, Norway, independently discovered the genetic cause of KWE in Norwegians. Ramsay and Fiskerstrand collaborated. The different DNA duplications in the South African and Norwegian families overlapped at a critical genomic region called an enhancer (which 'switches on' the gene) providing strong evidence that this was, in fact, the KWE mutation.

For over a year the scientists researched how this duplicated enhancer caused KWE. They demonstrated that the mutation causes a nearby gene to produce more protein than normal and that this abnormal expression was the likely cause of the skin peeling. Exactly twenty years after determining that the KWE mutation lies on chromosome 8, the mutation that causes KWE was identified and published.

Solving the mystery of KWE was a journey of data analysis, ancestry mapping, genomic comparison and global collaboration. Ngcungcu continues her work as a postdoctoral fellow examining the genetics of another skin disorder, albinism, and as a lecturer in the Division of Human Genetics at Wits from July 2017.

Explore further: Gene ABL1 implicated in both cancer and a developmental disorder

More information: Thandiswa Ngcungcu et al. Duplicated Enhancer Region Increases Expression ofCTSBand Segregates with Keratolytic Winter Erythema in South African and Norwegian Families, The American Journal of Human Genetics (2017). DOI: 10.1016/j.ajhg.2017.03.012

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Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or 'Oudtshoorn skin', in Afrikaners.

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Researchers have undertaken the world's largest genetic study of childhood overgrowth syndromes - providing new insights into their causes, and new recommendations for genetic testing.

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Dr. John Walley Littlefield, Groundbreaking Geneticist Patch.com John Walley Littlefield, M.D., a renowned physician-scientist whose work dramatically advanced the field of genetics and touched countless human lives, died peacefully on Thursday, April 20, surrounded by his family and loved ones. He was 91. A former ...

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Dr. John Walley Littlefield, Groundbreaking Geneticist - Patch.com

Photo: Jan Chlebik for the ICR

Researchers have undertaken the worlds largest genetic study of childhood overgrowth syndromes providing new insights into their causes and new recommendations for genetic testing.

Overgrowth syndromes describe conditions that cause children to be taller and to have a bigger head size than expected for their age, and also to have an intellectual disability or other medical problems.

Scientists at The Institute of Cancer Research, London, found many of the children with overgrowth syndromes had mutations in one of 14 different genes.

They also showed that many of the overgrowth genes are also involved in driving cancer growth, though intriguingly the types of mutations involved in promoting human growth and cancer growth are often different.

The researchers collected samples and information from 710 children with an overgrowth syndrome through an international study, funded by Wellcome.

They used a technique called exome sequencing to analyse the DNA of all the genes in each child and discovered a genetic cause for their overgrowth syndrome in 50% of the children.

These children had genetic mutations in one of the 14 genes, and usually the mutation started in the child with the overgrowth syndrome and was not inherited from either parent.

Amongst the 14 genes was HIST1H1E, which has not been previously linked to a human disorder. The other genes have been linked with human disorders before, but their contribution to overgrowth syndromes was not known.

Importantly, the study showed that the major genes causing overgrowth syndromes are involved in epigenetic regulation, which means they control how and when other genes will be switched on and off.

Mutations in epigenetic regulation genes were the cause of overgrowth in 44% of the children in the study, which was published in theAmerican Journal of Human Genetics.

Study Leader Professor Nazneen Rahman, Head of Genetics at the ICR and The Royal Marsden NHS Foundation Trust, said: The control of growth is a fundamental process important in development and many diseases, including cancer. We are pleased our work has provided both new insights into the mechanisms that control growth and new strategies by which genetic testing can be used efficiently to diagnose children with overgrowth syndromes.

Co-study lead Dr Katrina Tatton-Brown, Reader in Clinical Genetics at St Georges, University of London, Consultant Geneticist at the ICR and the South West Thames Regional Genetics Service, St Georges University Hospitals NHS Foundation Trust, said: Our study suggests that offering an exome sequencing genetic test to children with overgrowth and intellectual disability would be a practical and worthwhile way to try to identify the cause of their problems. This would allow us to provide children with more personalised management and to give better information to families about risks to other members of the family.

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Study unravels the genetics of childhood 'overgrowth' - The Institute of Cancer Research