A cSNP map and database for human chromosome 21

Area of Science:

• Genomics
• Human Genetics
• Bioinformatics

Background:

• Complex genetic diseases are influenced by variations like single nucleotide polymorphisms (SNPs).
• Human chromosome 21 (HC21) has a completed genomic sequence with 225 annotated genes.
• Efficient identification and mapping of potential coding SNPs (cSNPs) are crucial for genetic studies.

Purpose of the Study:

• To create a comprehensive database and map of coding SNPs (cSNPs) for human chromosome 21 (HC21).
• To provide a valuable resource for investigating the genetic basis of complex diseases linked to HC21.
• To establish a validated bioinformatics approach for cSNP discovery.

Main Methods:

• Generated candidate cSNPs by aligning HC21 genomic sequence to ESTs and mRNAs using a novel SNP identification program.
• Employed multiple alignment of known HC21 genes against other human database entries.
• Conducted gene-targeted cSNP discovery.
• Developed a novel program for context-dependent SNP identification to differentiate true variations from sequencing errors or paralogous alignments.

Main Results:

• Identified 377 cSNPs on HC21, averaging approximately 1 SNP per 1.5 kb of transcribed sequence.
• The identified cSNPs cover 65% of the known genes on the chromosome.
• Bioinformatics approach demonstrated a 78% confirmation rate for predicted cSNPs, with 32% confirmed overall.
• Established the first chromosome-specific cSNP map for HC21.

Conclusions:

• The HC21 cSNP database and map represent a significant resource for genetic research.
• These SNPs can be utilized to explore the contribution of HC21 loci to complex diseases such as bipolar affective disorder.
• The findings enable the study of allele-specific contributions to phenotypes associated with Down syndrome.