美国南加州大学日前发表公报称,该大学研究人员和中国北京协和医学院的同行合作,发现一种染色体异常能导致全身毛发过度生长,即俗称的“毛人”。
“毛人”是一种罕见的遗传疾病,学名为先天性多毛症。男性患者整个脸部、包括眼睑以及上半身长满毛发,而女性全身都长满毛发。研究人员称,他们的发现将有助于开发抑制毛发过度生长的新疗法,也可能帮助找到秃顶的新疗法。
以协和医学院张学教授为首的这个研究小组在新一期《美国人类遗传学期刊》发表论文说,张学等中方研究人员在为中国一个家庭进行检查时,首先发现了这种导致毛发过度生长的遗传现象。美方研究人员也在一个墨西哥家庭中发现了类似的遗传现象。
在中方的研究中,张学等人首先发现患者的5号染色体有一段插入了X染色体。在这一成果的启示下,美方研究人员发现,墨西哥患者X染色体的相同部位被4号染色体的一段插入。
研究人员解释说,当X染色体被其他染色体的“外来”DNA序列插入时,位于X染色体上的某个基因可能被“激活”,从而刺激毛发生长,导致先天性多毛症。他们认为,与毛发生长有关的SOX3基因可能起到了关键作用。
早些时候,科学家发现先天性多毛症属家族隔代遗传,其症状可能多代以后才重复出现。美方研究人员帕特尔说,刺激毛发生长的遗传信息很可能一直存在于基因组中,不过没有表达。如果进一步的研究能证实插入某段序列可以激活基因、刺激毛发生长,未来人们可望据此寻找治疗秃顶和遏制毛发过度生长的新方法。(生物谷Bioon.com)
生物谷推荐原文出处:
The American Journal of Human Genetics DOI:10.1016/j.ajhg.2011.05.004
X-Linked Congenital Hypertrichosis Syndrome Is Associated with Interchromosomal Insertions Mediated by a Human-Specific Palindrome near SOX3
Hongwen Zhu1, 2, 9, Dandan Shang1, 9, Miao Sun1, 9, Sunju Choi3, 9, Qing Liu1, Jiajie Hao4, Luis E. Figuera5, Feng Zhang6, Kwong Wai Choy7, Yang Ao1, Yang Liu8, Xiao-Lin Zhang1, Fengzhen Yue2, Ming-Rong Wang4, Li Jin6, Pragna I. Patel3, 9, Tao Jing2, 9 and Xue Zhang
X-linked congenital generalized hypertrichosis (CGH), an extremely rare condition characterized by universal overgrowth of terminal hair, was first mapped to chromosome Xq24-q27.1 in a Mexican family. However, the underlying genetic defect remains unknown. We ascertained a large Chinese family with an X-linked congenital hypertrichosis syndrome combining CGH, scoliosis, and spina bifida and mapped the disease locus to a 5.6 Mb critical region within the interval defined by the previously reported Mexican family. Through the combination of a high-resolution copy-number variation (CNV) scan and targeted genomic sequencing, we identified an interchromosomal insertion at Xq27.1 of a 125,577 bp intragenic fragment of COL23A1 on 5q35.3, with one X breakpoint within and the other very close to a human-specific short palindromic sequence located 82 kb downstream of SOX3. In the Mexican family, we found an interchromosomal insertion at the same Xq27.1 site of a 300,036 bp genomic fragment on 4q31.2, encompassing PRMT10 and TMEM184C and involving parts of ARHGAP10 and EDNRA. Notably, both of the two X breakpoints were within the short palindrome. The two palindrome-mediated insertions fully segregate with the CGH phenotype in each of the families, and the CNV gains of the respective autosomal genomic segments are not present in the public database and were not found in 1274 control individuals. Analysis of control individuals revealed deletions ranging from 173 bp to 9104 bp at the site of the insertions with no phenotypic consequence. Taken together, our results strongly support the pathogenicity of the identified insertions and establish X-linked congenital hypertrichosis syndrome as a genomic disorder.