Affiliations: Manovikas Biomedical Research and Diagnostic Centre,
MRIH, Kolkata, India
Note: [] Corresponding author: Kanchan Mukhopadhyay, Manovikas Biomedical
Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass,
Kolkata – 700107, India. Tel.: +91 033 4001 9179; Fax: +91 033 2442 8275;
E-mail: kanchanmvk@yahoo.com; mvk_km@yahoo.co.in
Abstract: Trisomy of the 21{st} 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 21{st} 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. ETS2 rs461155 showed
high heterozygosity in DS. Significantly lower frequency of SIM2 C-G
haplotype (rs2073601-rs2073416) was noticed in individuals with DS (P value
=0.01669) and their fathers (P value=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 (P value
=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.
Keywords: Down syndrome, ETS2, SIM2, transcriptional regulation
