Deciphering genetic disease in the genomic era: the model of GnRH deficiency.
Deciphering genetic disease in the genomic era: the model of GnRH deficiency.
复制标题
DOI：
10.1126/scitranslmed.3000288
复制
发表时间：
2010-05-19
影响因子：
17.1
通讯作者：
Crowley WF Jr
中科院分区：
文献类型：
--
作者：
Sykiotis GP;Pitteloud N;Seminara SB;Kaiser UB;Crowley WF Jr
先天性促性腺激素释放激素（GnRH）缺乏症是一种可治疗的，但罕见的生殖失败，已揭示了控制人类生殖的生理机制，但尽管在发现致病性单基因缺陷方面取得了实质性进展，但GnRH缺乏症的遗传基础仍然未知。虽然受影响的家庭的公正的遗传学调查已确定突变的新基因作为这种疾病的原因，他们的应用已受到严重限制，因为GnRH缺乏症对生育能力的负面影响;此外，相对较少的许多候选基因提名，因为在体外或动物模型实验的生物相容性，随后在患者中得到验证。随着测序、纯合性作图和全基因组水平结构变异检测等激动人心的技术平台的出现，人类研究再次成为基因发现的主导。以人类GnRH缺乏为范例，我们讨论了以患者为中心的临床遗传学研究的新兴模式及其在不久的将来与基本方法的互补性。
Congenital gonadotropin-releasing hormone (GnRH) deficiency is a treatable albeit rare form of reproductive failure that has revealed physiological mechanisms controlling human reproduction, but despite substantial progress in discovering pathogenic single-gene defects, most of the genetic basis of GnRH deficiency remains uncharted. Although unbiased genetic investigations of affected families have identified mutations in novel genes as causes of this disease, their application has been severely limited because of the negative effect of GnRH deficiency on fertility; moreover, relatively few of the many candidate genes nominated because of biological plausibility from in vitro or animal model experiments were subsequently validated in patients. With the advent of exciting technological platforms for sequencing, homozygosity mapping, and detection of structural variation at the whole-genome level, human investigations are again assuming the leading role for gene discovery. Using human GnRH deficiency as a paradigm, we discuss the emerging model of patient-focused clinical genetic research and its complementarities with basic approaches in the near future.
登录
查看更多内容
DOI：
10.1038/nrendo.2009.177
发表时间：
2009-10
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.8
作者：
Dodé, C;Levilliers, J;Hardelin, JP
通讯作者：
Hardelin, JP
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
56.9
作者：
KAJIWARA, K;BERSON, EL;DRYJA, TP
通讯作者：
DRYJA, TP
影响因子：
13.6
作者：
Hoefele, Julia;Wolf, Matthias T. F.;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm