Centromere reference models for human chromosomes X and Y satellite arrays.
Centromere reference models for human chromosomes X and Y satellite arrays.
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DOI：
10.1101/gr.159624.113
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发表时间：
2014-04
期刊：
影响因子：
7
通讯作者：
Kent WJ
中科院分区：
文献类型：
--
作者：
Miga KH;Newton Y;Jain M;Altemose N;Willard HF;Kent WJ
人类基因组序列仍然不完整，存在代表内源性着丝粒和其他异染色质区域的数兆酶大小的间隙。现有的基于序列的研究表明，这些位点在着丝粒功能和染色体配对中起作用，这是确保细胞分裂过程中染色体分离的必要条件。这些区域的一个共同的基因组特征是富含几乎相同的串联重复序列的长阵列，称为卫星dna，它提供了有限数量的变异位点，以区分数百万个碱基中的单个重复拷贝。这种实质性的序列同质性挑战了现有的组装策略，因此，在正在进行的基因组研究中忽略了着丝粒区域。为了解决这个问题，我们利用从全基因组霰弹枪读取获得的单体序列和排序信息来模拟X和Y染色体上的两个单倍体人类卫星阵列，从而在单个基因组中初步表征了3.83 Mb的着丝粒DNA。为了进一步扩大每个着丝粒参考序列模型的效用，我们评估了阵列内的位点的短读映射性和染色体特异性。由于卫星dna以协调一致的方式进化，我们使用这些着丝粒组合来评估来自不同人群的366个个体的序列变异程度。因此，我们确定了X和Y着丝粒中的两个卫星阵列变体，由阵列长度和序列组成决定。本研究提供了区域着丝粒的初始序列表征，并为将基因组表征扩展到这些位点以及复杂基因组中其他重复序列丰富的区域奠定了基础。
The human genome sequence remains incomplete, with multimegabase-sized gaps representing the endogenous centromeres and other heterochromatic regions. Available sequence-based studies within these sites in the genome have demonstrated a role in centromere function and chromosome pairing, necessary to ensure proper chromosome segregation during cell division. A common genomic feature of these regions is the enrichment of long arrays of near-identical tandem repeats, known as satellite DNAs, which offer a limited number of variant sites to differentiate individual repeat copies across millions of bases. This substantial sequence homogeneity challenges available assembly strategies and, as a result, centromeric regions are omitted from ongoing genomic studies. To address this problem, we utilize monomer sequence and ordering information obtained from whole-genome shotgun reads to model two haploid human satellite arrays on chromosomes X and Y, resulting in an initial characterization of 3.83 Mb of centromeric DNA within an individual genome. To further expand the utility of each centromeric reference sequence model, we evaluate sites within the arrays for short-read mappability and chromosome specificity. Because satellite DNAs evolve in a concerted manner, we use these centromeric assemblies to assess the extent of sequence variation among 366 individuals from distinct human populations. We thus identify two satellite array variants in both X and Y centromeres, as determined by array length and sequence composition. This study provides an initial sequence characterization of a regional centromere and establishes a foundation to extend genomic characterization to these sites as well as to other repeat-rich regions within complex genomes.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.4
作者：
MAHTANI, MM;WILLARD, HF
通讯作者：
WILLARD, HF
影响因子：
3.3
作者：
Luce, Amy C.;Sharma, Anupma;Dawe, R. Kelly
通讯作者：
Dawe, R. Kelly
影响因子：
1.6
作者：
ALEXANDROV, IA;MITKEVICH, SP;YUROV, YB
通讯作者：
YUROV, YB
影响因子：
7
作者：
Mahtani, MM;Willard, HF
通讯作者：
Willard, HF