一个新的小鼠被毛突变位点 (Uncv)的高分辨遗传图谱和物理图谱的构建(英文)  

A High-resolution Genetic and Physical Map of a Mouse Coat Abnormity Locus ( Uncv )

作　　者：史耀舟[1] 王冬平[2] 胡兰靛[3] 赵国屏[3] 王玉珍[1] 孔祥银[3] 李善如[2] 

机构地区：[1]中国科学技术大学生命科学学院,合肥230027 [2]军事医学科学院实验动物中心,北京100071 [3]中国科学院上海生命科学研究院生物工程研究中心,上海200233

出　　处：《生物化学与生物物理学报》2003年第5期397-402,共6页

基　　金：国家自然科学基金资助项目 (No .3 95 0 0 0 78,No.3 9970 3 90 );国家高技术研究发展计划 ( 863计划 )资助项目 (No .2 0 0 1AA2 2 10 91);国家杰出青年基金资助项目 (No .3 0 12 5 0 2 8)~~

摘　　要：迄今为止 ,人们已经发现了 10 0多个影响小鼠和人的毛发发育的基因 ,在以前的研究中 ,Uncv被证实是一个新的影响小鼠被毛的位点 ,具体表现为纯合突变体为无毛 ,杂合突变体表现为稀毛。除此之外 ,纯合的突变体还表现为生长和发育的迟缓。克隆这一突变基因将有助于更好地了解人类毛发发育异常相关的疾病。尽管这一位点已经被定位在小鼠 11号染色体上 ,但是没有该区域的精细遗传图谱和物理图谱直接克隆该基因有一定的难度。利用了两组杂交方式 ,[BALB/c(Uncv/Uncv)×C3H (+/+) ]×BALB/c (Uncv/Uncv)和 [BALB/c (Uncv/Uncv)×C5 7BL/6 (+/+) ]×BALB/c(Uncv/Uncv) ,共 2 0 74个F2代个体 ,通过对 11号染色体上的 16个微卫星标记的基因分型连锁分析 ,最终把该基因定位于11号染色体上位于D11Mit337和D11Mit338之间的约 1.4cM之间的区域。随后 ,利用BAC文库杂交和BAC末端序列PCR锚定的方法 ,构建了由 35个BAC构成的高分辨的BAC重叠群 ,这一高分辨的遗传图谱和物理图谱的构建 ,为进一步克隆这一突变基因打下了基础。More than a hundred of loci (genes) affect the development of mouse and human hair. A locus of Uncv (uncovered) has been confirmed to be involved in hairlessness for homozygote and sparse hair for heterozygote. Except hairlessness(or called uncovered coat), the homozygote was also accompanied by growth retard and puberty delay. Identification of the mutation in the gene will be important for understanding the related diseases in human. Although the uncovered locus (Uncv) has been mapped to the mouse distal chromosome 11(Chr11), the high-resolution genetic map and physical map of the locus has not been created. In this study, 2074 F2 mouse populations from backcross [BALB/c (Uncv/Uncv) × C3H (+/+)]× BALB/c (Uncv/Uncv ) and [BALB/c (Uncv/Uncv )× C57BL/6 (+/+)] × BALB/c( Uncv/Uncv ) were genotyped using 16 polymorphic markers with an ≈20 cM interval on mouse distal Chr11. By genetic linkage analysis, Uncv locus was mapped to an ≈1.4 cM interval between markers D 11 Mit 337 and D11Mit338 with the following order: proximal D 11Mit 338- D 11 Mit203 (Uncv)- D 11 Mit103 - D11 Mit337 distal on mouse Chr11. And then, a contig of 35 BACs representing the Uncv- containing region was constructed. The contig covered 800-1000 kb region flanked by 189 K 10- SP 6 and D 11Mit 103. Together, we have constructed the high-resolution genetic map and detailed physical map of the Uncv region. This will facilitate the identification of the Uncv loci.

关 键 词：小鼠 毛发 突变 遗传图 物理图 人类 发育异常 

分 类 号：Q953[生物学—动物学]