Congenital heart disease (CHD) can affect up to 1% of live births, and despite abundant evidence of a genetic etiology, the genetic landscape of CHD is still not well understood. A large-scale mouse chemical mutagenesis screen for mutations causing CHD yielded a preponderance of cilia-related genes, pointing to a central role for cilia in CHD pathogenesis. The genes uncovered by the screen included genes that regulate ciliogenesis and cilia-transduced cell signaling as well as many that mediate endocytic trafficking, a cell process critical for both ciliogenesis and cell signaling. The clinical relevance of these findings is supported by whole-exome sequencing analysis of CHD patients that showed enrichment for pathogenic variants in ciliome genes. Surprisingly, among the ciliome CHD genes recovered were many that encoded direct protein–protein interactors. Assembly of the CHD genes into a protein–protein interaction network yielded a tight interactome that suggested this protein–protein interaction may have functional importance and that its disruption could contribute to the pathogenesis of CHD. In light of these and other findings, we propose that an interactome enriched for ciliome genes may provide the genomic context for the complex genetics of CHD and its often-observed incomplete penetrance and variable expressivity.

George C. Gabriel

Madhavi Ganapathiraju

Cecilia W. Lo

Annual Review of Genomics and Human Genetics

自 2000 年出版的《基因组学和人类遗传学年度回顾》涵盖了基因组学领域的重大发展，因为它们适用于人类遗传学和人类基因组。我们对基因组技术、基因组结构和功能、基因改造、人类变异和群体遗传学、人类进化以及更重要的是人类遗传疾病的各个方面以及包括个体化医学等领域都特别感兴趣。

Since its inception in 2000, the Annual Review of Genomics and Human Genetics has covered significant advancements in the field of genomics, particularly as they relate to human genetics and the human genome. We are particularly interested in various aspects of genomic technologies, genomic structure and function, genetic modification, human variation and population genetics, human evolution, and, importantly, human genetic diseases, including fields such as personalized medicine.

《Annual Review of Genomics and Human Genetics》自2000年出版以来，涵盖了基因组学领域的重要进展，特别是与人类遗传学和人类基因组相关的研究。我们关注基因组技术、基因组结构与功能、基因改造、人类变异与群体遗传学、人类进化，以及人类遗传疾病等多个方面，尤其是个体化医学等领域。

Category	Quartile
生物学	2
生物学, 遗传学	2

The Role of Cilia and the Complex Genetics of Congenital Heart Disease

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Category	Quartile
GENETICS & HEREDITY	1