regulate gene expression). (26, 27) But there are other, poorly-understood functional regions. Many non-coding regions are highly conserved across species, suggesting that they have a function. Gene expression can be altered by common, synonymous exonic SNPs (no coding change), and by SNPs in introns (non-coding gene segments).(28) Indeed, most genomic DNA is apparently transcribed into RNA and thus could have unknown regulatory functions.(29) Most rare SNP associations will be missed by current GWAS methods, but it is expected that the 1000 Genomes Project (www.1000genomes.org) will discover most SNPs with 1-5% frequencies, which would permit an extension of GWAS methods into that range. Linkage could detect a locus with rare pathogenic variants in many families.
