Integrated YAC contig map of the Prader-Willi/Angelman region on chromosome 15q11-q13 with average STS spacing of 35 kb
Integrated YAC contig map of the Prader-Willi/Angelman region on chromosome 15q11-q13 with average STS spacing of 35 kb
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DOI：
10.1101/gr.8.2.146
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发表时间：
1998-02-01
期刊：
影响因子：
7
通讯作者：
Ledbetter, DH
中科院分区：
文献类型：
--
作者：
Christian, SL;Bhatt, NK;Ledbetter, DH
Prader-Willi综合征和Angelman综合征与染色体15 q11-q13的双亲特异性异常相关，最常见的是类似于4-Mb区域的缺失。由于基因组印记，该区域的父亲缺陷导致PWS和母亲缺陷导致AS。此外，该区域还经常参与其他染色体重排，包括重复、三重或额外标记的形成。这一区域的物理图谱对于阐明基因组印记的基因和机制，以及理解重复性染色体印记的机制具有重要意义。初始YAC重叠群从D15 S18延伸到D15 S12，由23个YAC和21个STS组成，平均分辨率约为每200 kb一个STS。为了封闭该重叠群中的两个缺口，使用位于D15 S18和254 B5 R之间的缺口差距侧翼的两个STS和位于GABRA 5 - 149 A9 L缺口远端的三个STS进行YAC筛选。此外，我们开发了11个新的STS，包括7个多态性标记。虽然有几个小组已经开发出全基因组遗传和辐射杂交图谱，但15 q11-q13的覆盖深度有些有限，并且图谱之间存在标记顺序的差异。为了解决这一矛盾，并提供一个更详细的STS在该地区的地图顺序，我们已经构建了一个完整的YAC STS为基础的物理图谱15 q11-q13包含118 YAC和118 STS，其中包括38个STR和49个基因/EST。使用该区域大小的4 Mb的估计，该图提供了35 kb的平均STS间隔。该图谱为确定该区域的疾病基因提供了宝贵的资源，也为完整的DNA测序提供了框架。
Prader-Willi syndrome and Angelman syndrome are associated with parent-of-origin-specific abnormalities of chromosome 15q11-q13, most frequently a deletion of an similar to 4-Mb region. Because of genomic imprinting, paternal deficiency of this region leads to PWS and maternal deficiency to AS. Additionally, this region is Frequently involved in other chromosomal rearrangements including duplications, triplications or supernumerary marker Formation. A derailed physical map of this region is important For elucidating the genes and mechanisms involved in genomic imprinting, as well as for understanding the mechanism of recurrent chromosomal rearrangments. An initial YAC contig extended from D15S18 to D15S12 and was comprised of 23 YACs and 21 STSs providing an average resolution of about one STS per 200 kb. To close two gaps in this contig, YAC screening was performed using two STSs that flank the gap between D15S18 and 254B5R and three STSs located distal to the GABRA5-149A9L gap. Additionally, we developed 11 new STSs, including seven polymorphic markers. Although several groups have developed whole-genome genetic and radiation hybrid maps, the depth of coverage for 15q11-q13 has been somewhat limited and discrepancies in marker order exist between the maps. To resolve the inconsistencies and to provide a more detailed map order of STSs in this region, we have constructed an integrated YAC STS-based physical map of chromosome 15q11-q13 containing 118 YACs and 118 STSs, including 38 STRs and 49 genes/ESTs. Using an estimate of 4 Mb for the size of this region, the map provides an average STS spacing of 35 kb. This map provides a valuable resource for identification of disease genes localized to this region as well as a framework For complete DNA sequencing.