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小鼠5号染色体上显性白斑(W)区域的遗传分析:W附近克隆DNA标记的鉴定

Genetic analysis of the dominant white-spotting (W) region on mouse chromosome 5: identification of cloned DNA markers near W.

作者信息

Geissler E N, Cheng S V, Gusella J F, Housman D E

机构信息

Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.

出版信息

Proc Natl Acad Sci U S A. 1988 Dec;85(24):9635-9. doi: 10.1073/pnas.85.24.9635.

Abstract

We have assigned several mouse cDNA and genomic clones to the W region of mouse chromosome 5, established their position with respect to various marker loci in the region, and provided molecular verification that the W19H mutation is a deletion. Meiotic recombination analysis of an interspecific mouse backcross indicated the following gene order and distances [in centimorgans (cM)]: centromere-Emv-1-(13 cM)-D4S76-(17 cM)-D5SC25-(5 cM)-alpha-casein-(1 cM)-beta- casein-(6 cM)-alpha-fetoprotein-(18 cM)-beta-glucuronidase. D5SC25, an anonymous locus defined by a mouse brain cDNA, maps near the map position of W and within the breakpoints of the presumed genetic deletion that causes the W19H phenotype. Southern analysis of DNAs of W19H/+ interspecific F1 hybrid mice and somatic cell hybrid lines carrying the W19H deletion chromosome showed the deletion of D5SC25. In fact, analysis of other mutations at or near the W locus, which had been transferred from the strain of origin for many backcross generations, revealed the retention of donor restriction fragment length polymorphisms at the D5SC25 locus. Such evidence confirms close linkage between D5SC25 and W (within 1 cM) and indicates that the D5SC25 cDNA clone could serve as a starting point in a chromosome "walk" to W and other closely linked loci that affect development.

摘要

我们已将几个小鼠cDNA和基因组克隆定位到小鼠5号染色体的W区域,确定了它们相对于该区域各种标记位点的位置,并提供了分子证据证明W19H突变是一种缺失。种间小鼠回交的减数分裂重组分析表明了以下基因顺序和距离[以厘摩(cM)计]:着丝粒-Emv-1-(13 cM)-D4S76-(17 cM)-D5SC25-(5 cM)-α-酪蛋白-(1 cM)-β-酪蛋白-(6 cM)-甲胎蛋白-(18 cM)-β-葡萄糖醛酸酶。D5SC25是一个由小鼠脑cDNA定义的无名位点,定位在W的图谱位置附近以及导致W19H表型的假定基因缺失的断点范围内。对携带W19H缺失染色体的W19H/+种间F1杂种小鼠和体细胞杂种系的DNA进行Southern分析,结果显示D5SC25缺失。事实上,对W位点或其附近已从起源品系转移了许多回交世代的其他突变进行分析,发现D5SC25位点保留了供体限制性片段长度多态性。这些证据证实了D5SC25与W之间紧密连锁(在1 cM范围内),并表明D5SC25 cDNA克隆可作为向W及其他影响发育的紧密连锁位点进行染色体“步移”的起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8847/282821/9a9df818d6a7/pnas00303-0274-a.jpg

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