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Genetic Significance of the Ashkenazi Jewish Population in Relation to Disease, Coursework Example

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Coursework

The research article Implications for Health and Disease in the Genetic Signature of the Ashkenazi Jewish Population describes the effect of genetics on individuals in the Ashkenazi Jewish community.  Certain genetic diseases, such as Tai-Sach’s disease, have a high prevalence  among the Ashkenazi Jewish population; this is attributed to their genetic homogeneity and a high amount of intermarrying within the community.  Because of their common origin in the Eastern European Rhine valley, and exhibition of the founder effect, bottlenecking, and genetic drift, the Ashkenazi Jewish population is susceptible to many genetic diseases.  Founder effects are distinctly displayed in both mitochondrial and Y-chromosome lineage.

The study used the Ashkenazi Jewish population to study the relevance of genetics in relation to complex inherited diseases.  It differentiated the founder effects and genetic drift experienced by the Ashkenazi Jewish population in relation to people of the same region who were not of the Ashkenazi Jewish population, and Americans.  Single nucleotide polymorphism markers (SNP) were used to examine how pathologies were related to specific genes from a large cohort of unselected Ashkenazi Jewish people from Israel.  SNP microarrays evaluated the differing nucleotide sequences.  Allele patterns specific to autosomal markers in the Ashkenazi Jewish population were analyzed.

The results found that there was a greater amount of genes which facilitated the transepithelial chloride transport in the Ashkenazi Jewish population.  This evidence may serve as a potential explanation why the Ashkenazi Jewish population experience a higher number of inherited disorders such as cystic fibrosis, Usher syndrome, Tai-Sach’s disease, and other autoimmune and metabolic disorders.

Samples were collected from three sources: Ashkenazi Jewish individuals recruited from Israeli blood banks, the human genome diversity panel (HGDP) database, and Caucasian subjects from Duke University.  Each subject was genotyped and quality control methods were used to organize the data.  Common ancestry was estimated with a population structure analysis, which was performed using the maximum likelihood based ADMIXTURE program.  A genome-wide association study (GWAS) methods was used to examine the relationship of the Ashkenazi Jewish genetic variation to ancestry information markers and the biology of health and disease.  This quantitative method was performed based on the ADMIXTURE data with samples with high SNP scores.  An Association list GO annotator (ALIGATOR) assessed whether any biologically relevant pathways were over-represented among the list of SNPs.  The ALIGATOR characterizes genes with respect to their gene ontology (GO) categories and is tests the SNP data and controls for the size of each gene and the number of SNPs present on the array.  The GO analysis shows allele frequency differences in multiple genes in pathways implicated by common diseases in the Ashkenazi Jewish population. The degree and probability of over-representation of specific GO categories is tested using the SNPs appearing above and below the GWAS limitations.  Results were further cemented with the GSA-SNP program which uses the gene-set enrichment-based analysis as opposed to the overrepresentation-based analysis of the ALIGATOR.  The GSA-SNP evaluates all SNPs in the analysis and ranks the gene sets in order of significance as opposed to a pre-specified measure.  When the overlapping markers were identified, a principal component analysis was performed and examined both inter-and intra-population distribution using EIGENSTRAT.  The distances between each population were calculated with GENEPOP v4.1 by a weighted analysis of variance (ANOVA).

The results of this study enhance prior research on genetic mutations which are found in high occurrence in the Ashkenazi Jewish population.  Individuals in the Ashkenazi Jewish community are at high risk for developing certain devastating inherited disorders.  By better understanding genetic disorders in the Ashkenazi Jewish population, both prevention and treatment of many diseases will be possible.

 

References

Bray, S., Mulle, J., Dodd, A., Pulver, A., Wooding, S., & Warren, S. (2010). Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population. Proceedings of the National Academy of Sciences, 107(37), 16222-7. doi: 10.1073/pnas.1004381107

Guha, S., Rosenfeld, J., Malhotra, A., Lee, A., Gregersen, P., Kane, J., Pe-er, I., & Darvasi, A.

(2012). Implications for health and disease in the genetic signature of the Ashkenazi Jewish population. Genome Biology, 13(1), doi: 10.1186/gb-2012-13-1-r2

Ostrer, H., & Skorecki, K. (2013). The population genetics of the Jewish people. Human Genetics, 132(2), doi: 10.1007/s00439-012-1235-6

Tufts Medical Center. (2013). Ashkenazi Jewish diseases. Retrieved from http://www.tuftsmedicalcenter.org/OurServices/SpecialServicesandCenters/JewishGeneticDiseasesScreening/AshkenaziJewishDiseases

 

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