科學(xué)家報(bào)告了一個(gè)在普通人群中尋找與“好”膽固醇低有關(guān)的基因變異的新方法,。這個(gè)方法也能用于尋找與其他疾病有關(guān)的基因變異，有些變異靠研究有遺傳病史的小家族是很難找到的,?？茖W(xué)家說，“好”膽固醇特別低的人群,，比“好”膽固醇高的人群,，更可能攜帶導(dǎo)致遺傳性低“好”膽固醇的基因變異。“好”膽固醇指的是血液中的高密度膽固醇,，“好”膽固醇低的人得冠狀動(dòng)脈硬化的可能性更高,。這個(gè)結(jié)果顯示，常見疾病不一定總是和常見的基因變異有關(guān),，可能是罕見基因變異的強(qiáng)的表型效果,。

Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol
Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of highdensity lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16% versus 2%) in individuals with low HDL-C (<fifth percentile) than in those with high HDL-C (>95th percentile). Similar findings were obtained in an independent population, and biochemical studies indicated that most sequence variants in the low HDL-C group were functionally important. Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population.