Differences in allele frequencies

Scientific Publication © 2012 INFOVALLEY. www.infovalley.net.my Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population Livy Alex et al. (2012) Nature 57: 358–362 Full article published in: Nature is a highly respected medical-scientific publication. In 2002, Nature publication was the most frequently cited publication worlwide. Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. In this study, a large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective is to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multi-ethnic Malaysian population. The study was performed at the Molecular Research Laboratory in University Malaya. Published SNPs in ADH causing genes were evaluated in this population and any unusual trends were reported. A large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes were examined, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Both healthy subjects and clinically diagnosed ADH patients for 310 previously documented single nucleotide mutations or SNPs located in APOB, LDLR and PCSK9 genes were genotyped. Selection of SNPs was initiated by searching genes reported to be associated with ADH from known databases. Dutch Lipid Clinic Network (DLCN) criteria for the diagnosis of heterozygous FH were employed for the selection of study subjects. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Validation of this study enables clinician to have alternative to diagnose patients of suspected FH using INFOHaem microarray chip FH1536 TM instead of the conventional method of Lipid Profile test. Design of INFOHaem microarray chip according to Asian populations Genotyping performed using Ilumina GoldenGateGenotyping (GGGT) Microarray Assay.

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Design of INFOHaem microarray chip according to Asian populations

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Page 1: Differences in allele frequencies

Scientific Publication

Differences in allele frequencies of autosomal dominant

hypercholesterolemia SNPs in the Malaysian population

Livy Alex et al. (2012) Nature 57: 358–362

Full article published in:

Nature is a highly respected medical-scientific publication. In 2002, Nature publication was the most frequently cited publication worlwide.

Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. In this study, a large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective is to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multi-ethnic Malaysian population. The study was performed at the Molecular Research Laboratory in University Malaya. Published SNPs in ADH causing genes were evaluated in this population and any unusual trends were reported. A large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes were examined, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Both healthy subjects and clinically diagnosed ADH patients for 310 previously documented single nucleotide mutations or SNPs located in APOB, LDLR and PCSK9 genes were genotyped.

Selection of SNPs was initiated by searching genes reported to be associated with ADH from known databases. Dutch Lipid Clinic Network (DLCN) criteria for the diagnosis of heterozygous FH were employed for the selection of study subjects. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Validation of this study enables clinician to have alternative to diagnose patients of suspected FH using INFOHaem microarray chip FH1536TM instead of the conventional method of Lipid Profile test.

Design of INFOHaem microarray chip according to Asian populations

Genotyping performed using Ilumina GoldenGateGenotyping (GGGT) Microarray Assay.