Abstract
ABSTRACTBackgroundKnowledge of the genetic background of many human diseases is currently lacking from genetically undiscovered regions, including Central Asia. Kazakhstan is the first Central Asian country where the genetic studies of Parkinson's disease (PD) have been emerging since it had become a member of the International Parkinson Disease Genomics Consortium. Here we report on the results of whole‐exome sequencing (WES) in 50 young‐onset PD (YOPD) cases from Kazakhstan.MethodologyWES was performed on 50 unrelated individuals with YOPD from Kazakhstan. Exome data were screened for novel/ultra‐rare deleterious variants in known and candidate PD genes. Copy number variants and small indels were also called.ResultsOnly three cases (6%) were found to be positive for known PD genes including two unrelated familial PD cases with LRRK2 p.(Arg1441Cys) and one case with a homozygous pathogenic PRKN p.(Arg84Trp) variant. Four cases had novel and ultra‐rare variants of uncertain significance in LRRK2, DNAJC13, and VPS35. Novel deleterious variants were found in candidate Mendelian PD genes including CSMD1, TNR, EIF4G1, and ATP13A3. Eight cases harbored the East Asian‐specific LRRK2 p.(Ala419Val) variant.ConclusionsThe low diagnostic yield in our study might imply that a significant proportion of YOPD cases in Central Asia remains unresolved. Therefore, a better understanding of the genetic architecture of PD among populations of Central Asian ancestry and the pathogenicity of numerous rare variants should be further investigated. WES is a valuable technique for large‐scale YOPD genetic studies in Central Asia.
Highlights
The studies of genetic association with the disease have predominantly been performed in European populations
While the results of this screening will be available in due time, to get an unprecedented glimpse of the genetic background of Central Asian Parkinson's disease (PD), here we report the findings from whole-e xome sequencing (WES) in young-o nset PD (YOPD) from Kazakhstan
Genetic diversity in Central Asia is among the highest in Eurasia making this region appealing for launching genetic studies including PD genetics (Comas et al, 2004)
Summary
The studies of genetic association with the disease have predominantly been performed in European populations. The under-representation of ethnically diverse populations precludes our ability to fully understand the genetic architecture of human disease and worsens health inequalities. This has been gaining particular importance in the field of Parkinson's disease (PD) genetics. While the results of this screening will be available in due time, to get an unprecedented glimpse of the genetic background of Central Asian PD, here we report the findings from whole-e xome sequencing (WES) in young-o nset PD (YOPD) from Kazakhstan. Kazakhstan is the first Central Asian country where the genetic studies of Parkinson's disease (PD) have been emerging since it had become a member of the International Parkinson Disease Genomics Consortium. WES is a valuable technique for large-scale YOPD genetic studies in Central Asia
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