Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project
Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project
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DOI：
10.1016/j.ajhg.2008.01.011
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发表时间：
2008-03-01
影响因子：
9.8
通讯作者：
Morton, Cynthia C.
中科院分区：
文献类型：
--
作者：
Higgins, Anne W.;Alkuraya, Fowzan S.;Morton, Cynthia C.
患有严重先天异常的个体中明显平衡的染色体重排代表了基因破坏和失调的自然实验。可以对这些个体进行研究，以确定对人类发育至关重要的新基因，并进一步注释已知基因的功能。这些基因的鉴定和表征是发育基因组解剖学计划（DGAP）的目标。 DGAP 是一项多学科努力，利用人类基因组计划的最新进展来增进我们对出生缺陷和人类发育过程的了解。参加 DGAP 的个体的临床显着表型各不相同，并且在大多数情况下涉及多个器官系统。对这些个体染色体重排的研究通过使用 BAC 和 fosmids 的 FISH、阵列 CGH、Southern 印迹杂交、MLPA、RT-PCR 和抑制 PCR 绘制了 40 个染色体重排的 77 个断点。十八个染色体断点已被克隆并测序。检测到了意想不到的基因组失衡和神秘的重排，但频率低于之前报道的频率。患有多种先天性异常的个体的染色体重排（平衡和不平衡）仍然是基因发现和注释的宝贵资源。
Apparently balanced chromosomal rearrangements in individuals with major congenital anomalies represent natural experiments of gene disruption and dysregulation. These individuals can be studied to identify novel genes critical in human development and to annotate further the function of known genes, Identification and characterization of these genes is the goal of the Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort that leverages the recent advances resulting from the Human Genome Project to increase our understanding of birth defects and the process of human development. Clinically significant phenotypes of individuals enrolled in DGAP are varied and, in most cases, involve multiple organ systems. Study of these individuals' chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40 chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern-blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and cryptic rearrangements were detected, but less frequently than has been reported previously. Chromosomal rearrangements, both balanced and unbalanced, in individuals with multiple congenital anomalies continue to be a valuable resource for gene discovery and annotation.