title: Prenatal detection of aneuploidy and imbalanced chromosomal arrangements by massively parallel sequencing.
abstract: Fetal chromosomal abnormalities are the most common reasons for invasive prenatal testing. Currently, G-band karyotyping and several molecular genetic methods have been established for diagnosis of chromosomal abnormalities. Although these testing methods are highly reliable, the major limitation remains restricted resolutions or can only achieve limited coverage on the human genome at one time. The massively parallel sequencing (MPS) technologies which can reach single base pair resolution allows detection of genome-wide intragenic deletions and duplication challenging karyotyping and microarrays as the tool for prenatal diagnosis. Here we reported a novel and robust MPS-based method to detect aneuploidy and imbalanced chromosomal arrangements in amniotic fluid (AF) samples. We sequenced 62 AF samples on Illumina GAIIx platform and with averagely 0.01× whole genome sequencing data we detected 13 samples with numerical chromosomal abnormalities by z-test. With up to 2× whole genome sequencing data we were able to detect microdeletion/microduplication (ranged from 1.4 Mb to 37.3 Mb of 5 samples from chorionic villus sampling (CVS) using SeqSeq algorithm. Our work demonstrated MPS is a robust and accurate approach to detect aneuploidy and imbalanced chromosomal arrangements in prenatal samples.
authors.affiliation: Department of Perinatal Medicine, Beijing Obstetrics and Gynecology Hospital - Capital Medical University, Beijing, China. sd_bao@sina.com
authors.forename: Shan
authors.initials: S
authors.lastname: Dan
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Fuman
authors.initials: F
authors.lastname: Jiang
authors.forename: Jingrong
authors.initials: J
authors.lastname: Lin
authors.forename: Zhaoling
authors.initials: Z
authors.lastname: Xuan
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shengpei
authors.initials: S
authors.lastname: Chen
authors.forename: Xuchao
authors.initials: X
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Tak Yeung
authors.initials: TY
authors.lastname: Leung
authors.forename: Tze Kin
authors.initials: TK
authors.lastname: Lau
authors.forename: Yue
authors.initials: Y
authors.lastname: Su
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000782:Aneuploidy; D025063:Chromosome Disorders / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*