Abstract
Trisomy of the 21st chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21st chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N= 132), their parents (N= 209) and ethnically matched controls (N= 149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses.ETS2rs461155 showed high heterozygosity in DS. Significantly lower frequency ofSIM2C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (Pvalue = 0.01669) and their fathers (Pvalue = 0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (Pvalue = 0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 ‘A’ allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population.
Highlights
Down syndrome (DS) (MIM# 190685) is the most common cause of intellectual disability throughout the world [1]
Trisomy of the 21st chromosome (HSA21) as a whole or triplication of genes in the Down syndrome critical region, leading to an over expression of these genes, may be one of the key factor for DS [2], it is still uncertain whether DS and its associated physiological abnormalities could be caused by particular gene loci in HSA21 [3]
Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) are two transcription factors located in HSA21 and are over expressed in individuals with DS [1]
Summary
Down syndrome (DS) (MIM# 190685) is the most common cause of intellectual disability throughout the world [1]. Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) are two transcription factors located in HSA21 and are over expressed in individuals with DS [1]. Downstream genes of these TFs are thought to play important roles in DS associated patho-physiology [1]. Higher differential expression ratio observed for the TFs in different tissues made them important candidates for disease association studies [4]
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