Dataset Information

Characterization of chromosomal abnormalities in pregnancy losses reveals critical genes and loci for human early development.

ABSTRACT: Detailed characterization of chromosomal abnormalities, a common cause for congenital abnormalities and pregnancy loss, is critical for elucidating genes for human fetal development. Here, 2,186 product-of-conception samples were tested for copy-number variations (CNVs) at two clinical diagnostic centers using whole-genome sequencing and high-resolution chromosomal microarray analysis. We developed a new gene discovery approach to predict potential developmental genes and identified 275 candidate genes from CNVs detected from both datasets. Based on Mouse Genome Informatics (MGI) and Zebrafish model organism database (ZFIN), 75% of identified genes could lead to developmental defects when mutated. Genes involved in embryonic development, gene transcription, and regulation of biological processes were significantly enriched. Especially, transcription factors and gene families sharing specific protein domains predominated, which included known developmental genes such as HOX, NKX homeodomain genes, and helix-loop-helix containing HAND2, NEUROG2, and NEUROD1 as well as potential novel developmental genes. We observed that developmental genes were denser in certain chromosomal regions, enabling identification of 31 potential genomic loci with clustered genes associated with development.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5671119 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Characterization of chromosomal abnormalities in pregnancy losses reveals critical genes and loci for human early development.

Chen Yiyun Y Bartanus Justin J Liang Desheng D Zhu Hongmin H Breman Amy M AM Smith Janice L JL Wang Hua H Ren Zhilin Z Patel Ankita A Stankiewicz Pawel P Cram David S DS Cheung Sau Wai SW Wu Lingqian L Yu Fuli F

Human mutation 20170329 6

Detailed characterization of chromosomal abnormalities, a common cause for congenital abnormalities and pregnancy loss, is critical for elucidating genes for human fetal development. Here, 2,186 product-of-conception samples were tested for copy-number variations (CNVs) at two clinical diagnostic centers using whole-genome sequencing and high-resolution chromosomal microarray analysis. We developed a new gene discovery approach to predict potential developmental genes and identified 275 candidat ...[more]

PMID: 28247551

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Project description:Fetal gastrointestinal tract obstruction (GITO) is the most frequently encountered gastrointestinal defect in the prenatal period. This study aimed to investigate the genetic disorders and pregnancy outcomes of fetal GITO. We reviewed data from 70 pregnancies that were referred for invasive prenatal testing because of fetal GITO. According to the level of obstruction, they were classified into esophageal atresia/stenosis, duodenal atresia/stenosis, jejunal or ileal atresia/stenosis, or anal atresia. Traditional karyotyping was performed on all the 70 pregnancies, and chromosomal microarray analysis (CMA) was performed on 32 of them in parallel. Traditional karyotyping revealed twelve (17.1%) chromosomal abnormalities, including 11 cases of trisomy 21 (Down syndrome), and one case of a supernumerary marker chromosome related to Cat eye syndrome. According to the absence or presence of other ultrasound anomalies, they were categorized into isolated GITO (n = 36) and non-isolated GITO (n = 34). The rate of chromosomal abnormalities in the non-isolated GITO pregnancies was significantly higher than that in the isolated GITO pregnancies (29.4 vs. 5.5%, p < 0.05); the survival rate in the isolated group was significantly higher than that in the non-isolated group (67.6 vs. 34.4%, p < 0.05). Among the 32 cases where CMA was performed, an additional one (3.1%) copy number variant with clinical significance was noted in a fetus with normal karyotype. The microduplication on 7q12 was considered to be the genetic etiology of duodenal stenosis, although it was inherited from a phenotypically normal mother. Our study supports the strong association between Down syndrome and fetal GITO, especially duodenal stenosis. Our findings suggested that the risk of chromosomal abnormalities was increased when GITO was accompanied by other ultrasound anomalies; thus, chromosomal abnormalities and fetal anatomy should be carefully evaluated for pregnancy management of fetal GITO.

Dataset Information

Characterization of chromosomal abnormalities in pregnancy losses reveals critical genes and loci for human early development.

Publications

Characterization of chromosomal abnormalities in pregnancy losses reveals critical genes and loci for human early development.

Similar Datasets

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