In a lengthy study, researchers have examined multiple generations of families in a particular population to uncover the impact of recently inherited DNA variations on recessive disease characteristics. This process has also led to the development of a population-specific database that contains unique DNA information not found in larger groups.
While you may have inherited physical traits from your parents, genetics goes much deeper than just outward appearances. Researchers at Baylor College of Medicine have spent over ten years studying families in a specific population to shed light on the influence of newly inherited DNA variants on recessive disease traits. This study has also resulted in the creation of a database specific to this population, which contains distinctive DNA information not seen in larger cohorts.Inherited DNA variations contribute to recessive disease traits and have led to the development of a population-specific database that contains unique DNA information not found in larger groups.
The results, recently featured in Genetics in Medicine OPEN, showed a connection between the occurrence of complex genetic disorders in families with higher levels of consanguinity compared to unaffected populations. Consanguinity occurs when both parents contribute similar genetic markers to their offspring, often by sharing a common ancestor, resulting in the inheritance of genetic information from both parents’ genomes.
“Our study found that individuals with a higher degree of parental consanguinity had longer regions of homozygosity (ROH) on the chromosome compared to those with less consanguinity,” said Dr. Zeynep Coban-Akdemir, a postdoctoral associate in molecular and human genetics at Baylor and currently an assistant professor at UTHealth School of Public Health. She is also a co-lead author on the study. “We can observe the effects of consanguinity as well as new genetic variations introduced into the family unit, representing more distant relationships within the clan or tribe.”ancestry and the impact of genetic variations on disease,” said Dr. Xun Gong, an assistant professor of molecular and human genetics at Baylor and co-lead author on the study. “For example, it presents a detailed analysis of genetic variations in patients with rare diseases, which can help in understanding the underlying genetic factors contributing to these diseases. Furthermore, it demonstrates the utility of statistical methods in assessing the impact of genetic variations on disease, providing valuable insights for future research in this area.” Gong also is co-lead author on the study.”Genetics and the application of various computational methods to understand these concepts is crucial,” explained Tugce Bozkurt-Yozgatli, a Ph.D. candidate at Acibadem University in Istanbul, Turkey.
Coban-Akdemir, who was part of the research conducted at the Lupski Lab at Baylor, emphasized the significance of the findings in revealing how genes function within different populations and clans, contributing to various recessive genetic disorders.
The study focused on a group of individuals from Turkey known to have different genetic markers compared to other European populations. The research aimed to investigate these genetic variations.The researchers conducted exome sequencing on 773 unrelated volunteers with suspected rare Mendelian diseases. They also created a database of genetic variants from this group and compared it to a database of 643 unaffected relatives. The study revealed that approximately half of the genetic variants in the Turkish group were not found in the larger European population.The article discusses the importance of including underrepresented populations in genetic databases. Dr. Coban-Akdemir and Dr. Pehlivan from Baylor College of Medicine highlight the unique genetic variations found in a group of Turkish individuals and families. They emphasize that these populations are not well-represented in larger databases and provide valuable insight into genetics that may be missed when focusing solely on European populations. This information could lead to a better understanding of genetic variations and their impact on health.
Crick base pair variations exist within our DNA. The Human Genome Project allowed researchers to explore the entire genomic DNA using next-generation sequencing technology. However, new challenges arose with these advances. It is difficult to determine which variant is causing disease out of the 40 million variations in our DNA. Studying healthy populations helps to eliminate many of these common variations from consideration. Therefore, we conducted a study on both patients and their healthy relatives in the Turkish population,” Pehlivan explained. “There are numerous changes in the genome, and we do not have a complete understanding of the mechanisms behind them.”The significance of all of these details is not fully understood, but the data gathered from this population study will be beneficial for researchers worldwide who are working to interpret the outcomes of other genetic variations in human DNA.”
Pehlivan recounted the process of collecting information and recruiting families for genomics research starting in 2010. They traveled long distances to rural areas where most of the patients lived, exemplifying a touching human interest story, to ensure that the database and clinical information would accurately represent these families.
“We have identified over 200 genes that have contributed to the existing pool of disease gene associations,are remarkably similar. By studying the genetic variations within different populations, we can gain a better understanding of the biological factors contributing to various diseases. This research not only has the potential to advance our knowledge of human biology and genome biology, but it could also lead to the development of nucleic acid treatments, similar to those used in the creation of the COVID vaccine. Ultimately, the findings from these studies have the potential to benefit a wide range of populations, making a significant impact on global health.” Pehlivan emphasized.
“The efforts of this research team extend beyond the specific population they have studied, with implications for diverse populations. Despite our differences, we share many genetic similarities. Therefore, the insights gained from this study can have far-reaching implications and benefit a wide range of individuals around the world.”statement really hammers home the importance of understanding genetic disorders to provide support for affected families worldwide. Dr. James R. Lupski, the Cullen Foundation Endowed Chair in Genetics and Genomics at Baylor, emphasized the shared humanity and similarities we all have, which underscores the significance of understanding how genetic disorders operate. Coban-Akdemir and Dr. Claudia M.B Carvalho have previously collaborated on studying gene variants to determine the underlying causes of diseases. This involves the production of modified proteins that may have a different function, shedding light on the mechanisms of genetic disorders.The researchers also focused on studying populations with and without genetic diseases. Their current research highlights the significance of diversity and inclusion as they continue to uncover the causes of genetic diseases. The work received support from the U.S. National Human Genome Research Institute/National Heart Lung and Blood Institute grant number UM1HG006542 for the Baylor Hopkins Center for Mendelian Genomics (BHCMG), as well as the U.S. National Human Genome Research Institute U01HG011758 for the Baylor College of Medicine for the Genomics Research to Elucidate the Genetics of Rare Disease consortium (BCM-GREGoR) and the National Institute of Neurological Disorders and Stroke.The study was supported by grants from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke (NINDS) R35NS105078, and the National Human Genome Research Institute U54-HG003273. J.E.P. received support from the NHGRI K08 HG008986.
Journal Reference:
- Zeynep Coban-Akdemir, Xiaofei Song, Francisco C. Ceballos, Davut Pehlivan, Ender Karaca, Yavuz Bayram, Tadahiro Mitani, Tomasz Gambin, Tugce Bozkurt-Yozgatli, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Lewis, Pengfei Liu, Eric Boerwinkle, Ada Hamosh, Richard A. Gibbs, V. Reid Sutton, Nara Sobreira, Claudia M.B. Carvalho, Chad A. Shaw, Jennifer E. Posey, David Valle, James R. Lupski. The impact of the study was significant and received support from various institutions.The impact of the Turkish population variome on the genetic makeup of rare diseases has been studied in Genetics in Medicine Open in 2024. The article can be found at DOI: 10.1016/j.gimo.2024.101830