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Archive - Oct 27, 2014

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Gene Duplications Associated with Autism Evolved Recently in Human History

Human geneticists have discovered that a region of the genome associated with autism contains genetic variation that evolved in the last 183,000 years, after the divergence of humans from ancient hominids, and likely plays an important role in autism and other diseases. The findings were presented on Saturday evening, October 18, at the opening of the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego, California. Researchers at the University of Washington analyzed the genomes of 2,551 humans, 86 great apes, one Neanderthal, and one Denisovan. The scientists closely examined a region of human chromosome 16 known as 16p11.2, where recurrent deletions and duplications that are major contributors to autism, and also associated with schizophrenia and extremes of body mass and head circumference, occur. Approximately 1% of individuals with simplex autism have deletions or duplication at 16p11.2. These events occur via nonallelic homologous recombination between directly oriented segmental duplications approximately 600 kilobase pairs apart, the presenter, Xander Nuttle, B.S., B.S.E., the first author of the report said. The research team found that certain segments of DNA in this region are repeated a variable number of times in different people and may also be associated with disease. To trace the origins of this variation, the researchers collaborated with colleagues at the University of Lausanne in Switzerland and the University of Bari in Italy to sequence and analyze corresponding regions of ape genomes. Mr.

Three Cystic Kidney Disease Genes Related to Hyperemesis Gravidarum (HG)

A possible genetic pathway related to hyperemesis gravidarum (HG), a severe form of morning sickness that affects Kate Middleton, wife of Prince William and mother of young Prince George (see photo), and 0.3 to 2% of all pregnancies, has been identified by Marlena Fejzo, Ph.D., an assistant researcher of hematology–oncology at the David Geffen School of Medicine at UCLA and an assistant professor of maternal and fetal medicine at the Keck School of Medicine of USC, and a team of colleagues. HG disease leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. Sixty years ago, HG was the cause of death in 10% of pregnancies, and, even today, it accounts for over 225,000 hospital discharges in the U.S. each year and 15% of HG-afflicted women in the U.S. choose therapeutic termination of pregnancy. The disease remains associated with significant maternal morbidity, including Wernicke’s encephalopathy, renal failure, kidney failure, liver function abnormalities, esophageal rupture, and post-traumatic stress. Genetics has long been thought to play a role in HG, but no definitive study had previously been done. Using exome sequencing in five HG pedigrees and over 470 controls, the Fejzo team identified three kidney disease genes [PKD1, polycystic kidney disease 1 (associated with 85% of autosomal dominant polycystic kidney disease in humans)], PKHD1 (polycystic kidney and hepatic disease 1, associated with autosomal recessive polycystic kidney and hepatic disease 1 in humans), and LAMA5 (laminin alpha 5, a hypomorphic mutation in this gene has been shown to cause polycystic kidney disease in mice) that were found to be variant in the HG families, but in none of the controls.