一項新的研究發(fā)現(xiàn)，單個基因拷貝數(shù)的不同對正常人之間的遺傳不同有大的影響,。科學家已經(jīng)知道人類遺傳的變異在很大程度上是與基因的復制和刪節(jié)有關(guān),。但是,，由于沒有針對在整個基因組掃描這種拷貝數(shù)多態(tài)性(copy number polymorphisms，簡稱CNPs)的技術(shù),，人們對CNPs對人類遺傳多樣性程度的影響所知甚少,。Jonathan Sebat和同事用代表性寡核苷酸微陣列分析(簡稱ROMA)產(chǎn)生了一個拷貝數(shù)差異的圖譜。這個圖顯示出CNPs很常見,，而且在人類基因組中廣泛分布,。作者觀察到了70各不同基因的拷貝數(shù)變化，這些基因與神經(jīng)功能,、細胞生長的調(diào)節(jié)、以及心陳代謝有關(guān),，還有的基因與某些疾病有關(guān),。
Large-Scale Copy Number Polymorphism in the Human Genome
The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.
Fig. 1. Genome-wide map of CNPs identified by ROMA. The position of all CNPs (excluding somatic differences) is shown. CNPs identified in multiple individuals (by Bgl II–ROMA) are indicated in yellow, and CNPs observed in only one individual are indicated in red. Additional CNPs identified by one Hind III–ROMA experiment are indicated in blue. Symbols denoting CNPs are not drawn to scale. Genome assembly gaps in pericentromeric and satellite regions are indicated by gray boxes. Genomic regions where recurring de novo rearrangements cause the developmental disorders Prader-Willi and Angelman syndromes, cat eye syndrome, DiGeorge/velocardiofacial syndrome, and spinal muscular atrophy are labeled A, B, C, and D, respectively.
Fig. 2. Validation of ROMA results by FISH. (A), (C), (E), and (G) show CNPs identified by ROMA and include the CNP identification number, the name of one gene located entirely within the interval, and the experiment name. (B), (D), (F), (H), and (I) show cytogenetic analyses of one or both individuals with probes that target the same CNP intervals. In all panels, the polymorphic probe is labeled red. In interphase cells [(B), (D), and (F)], a control probe (labeled green) was also included to confirm that cells were diploid. (B) CNP15 probe in GM11322 cells; (D) CNP56 probe in GM10470 cells; (F) CNP21 probe in GM10470 cells; (H) CNP32 probe in GM10540 cells; (I) CNP32 probe in SKN1 cells. In (I), one parental copy of chromosome 16 in SKN1 lacks the duplication (arrow).
