Researchers at Baylor College of Medicine conducted a study spanning more than a decade, looking at generations of families in a specific population to understand the role of newly inherited DNA variants in recessive disease traits. The study, published in Genetics in Medicine OPEN, found a correlation between occurrences of complex genetic disorders in families with increased levels of consanguinity, where both parents contribute similar genetic markers to an offspring, leading to longer regions of homozygosity in individuals with higher parental consanguinity. The researchers applied statistical methods to assess the impact of these genetic variations on disease and found that newly introduced genetic variations can better explain the clinical features observed in patients.
The study focused on a cohort of individuals from Turkey, known to have unique variations in genetic markers compared to other populations in Europe. The researchers created and analyzed a database of variants derived from exome sequencing of 773 unrelated volunteers affected with rare Mendelian disease traits, compared to 643 unaffected relatives. Roughly half of the genetic variants in the Turkish group were not present in greater European control populations, highlighting the unique genetic variation in this population. Dr. Davut Pehlivan emphasized the importance of studying healthy populations to understand the significance of genetic variations and their impact on disease, providing valuable insights for researchers globally.
The study identified more than 200 genes contributing to disease gene associations, shedding light on the underlying biological perturbations leading to a broad range of diseases. The researchers traveled to rural areas in Turkey to collect clinical information and data from families willing to participate in genomics research, ensuring an accurate representation of the population. Dr. Pehlivan highlighted the potential applications of the findings in advancing research in human biology and genome biology, ultimately benefiting patients and families by developing nucleic acid treatments similar to those used in the COVID vaccine.
Dr. James R. Lupski, the Cullen Foundation Endowed Chair in Genetics and Genomics at Baylor, emphasized the global impact of understanding genetic disorders, noting how genes act similarly across diverse populations despite individual differences. The researchers, including Dr. Zeynep Coban-Akdemir and Dr. Claudia M.B Carvalho, focused on studying variants of genes to identify disease causes through the production of altered proteins. Their work underscores the importance of diversity and inclusion in genetic research to elucidate the causes of genetic diseases and develop potential treatments.
The study was supported by grants from the U.S. National Human Genome Research Institute and the National Heart Lung and Blood Institute to the Baylor Hopkins Center for Mendelian Genomics, as well as other funding sources. The researchers’ findings provide valuable insights into the genetic underpinnings of rare diseases and demonstrate the potential for their work to impact diverse populations globally. By studying the genetic variations specific to the Turkish population, the researchers have advanced our understanding of genetic diseases and laid the groundwork for future research in human biology and genome biology.
