Gene-SNP haplotype analysis of an aging population

随着整个人类基因组现在几乎完全解码，人们的注意力转向了个体遗传变异。这种变异大部分由单核苷酸多态性（SNPs）组成，这可以解释遗传的个体间差异，例如疾病易感性和对药物的反应。衰老是大多数常见人类疾病的主要危险因素。鉴定候选基因中的snp并评估其对衰老相关表型的潜在功能影响，对于评估衰老的遗传成分（包括异常健康的衰老）至关重要。在这方面的最佳研究人群是那些与衰老相关的表型可以根据其从中年开始的进展来定义的人群，而不是作为时间快照。这项建议的目的是

With the entire human genome now almost completely decoded, attention is shifting towards individual genetic variation. Most of this variation consists of single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in, for example, disease susceptibility and response to medication. Aging is a major risk factor for most common human diseases. The identification of SNPs in candidate genes and the assessment of their potential functional impact on aging-related phenotypes will be important in assessing genetic components of aging, including exceptionally healthy aging. Optimal study populations in this respect are those in which aging-related phenotypes can be defined in terms of their progression from middle age onwards, rather than as snapshots in time. The objective of this proposal is to further optimize a previously developed SNP discovery method, Two-Dimensional Gene Scanning (TDGS), to comprehensively analyze SNPs in multiple candidate genes in large, aging populations. The validity of this approach will be assessed through association analysis, in a case control manner, of all possible SNPhaplotypes of a selection of nuclear and mitochondrial genes involved in musculoskeletal function in a population of 226 Mexican American individuals of an ongoing longitudinal study of aging (San Antonio Longitudinal Study of Aging; SALSA). The results are expected to enrich the ongoing study with a genetic component for this particular phenotype and to demonstrate the validity of TDGS as a high-throughput platform to screen aging populations for all possible SNPs in hundreds and ultimately thousands of candidate genes (comprehensive candidate approach).