FetalExome

FetalExome is a genetic test that analyzes and identifies known and potential disease-causing single nucleotide variants (SNVs) and small insertions and deletions (InDels) in nearly the entire protein-coding region of the genome (namely exome). In addition, FetalExome can also detect genome-wide absence of heterozygosity (AOH). FetalExome is ordered when prenatal ultrasound imaging detects an anomaly that strongly suggests that the fetal abnormality is caused by a monogenic disorder (by SNV or InDel). FetalExome is recommended to be performed in a trio setting and is often considered after a negative finding from chromosomal microarray analysis (CMA). Patients have the option to opt-out of reporting of secondary findings and carrier status for disease-causing genes.

Method: Genomic DNA (500-1000ng) extracted from the biopsied specimen is subjected to a non-target-enriched PCR-free library construction. The library is sequenced on NGS platforms including NovaSeq, HiSeq X Ten and BGISEQ-500/MGISEQ-2000. A minimal of 30X or 30-fold read-depth (~300 million read-pairs with 150-bp read length) are generated for each case. Reads are aligned to the reference sequence (GRCh37/hg19) using the Burrows-Wheeler Alignment tool (BWA) (PMID: 19451168). (1) SNVs calling is carried out by HaplotypeCaller (GATK) and annotated by ANNOVAR (PMID: 20601685) with different referenced databases. The analysis, interpretation, and reporting of variants will be confined to the exome. SNV interpretation is performed by referencing the medical literature and online databases according to the guidelines of the American College of Medical Genetics and Genomics. (2) For AOH detection, genotyping is carried out by analysis of mpileup file (Samtools), and regions (>5Mb as recommended by the American College of Medical Genetics and Genomics, ACMG; PMID: 32296163) with decreased rate of heterozygous SNVs and increased rate of homozygous SNVs are candidate AOHs.

Limitations: FetalExome does not exclude all chromosome anomalies such as trinucleotide repeat expansions, triploidy, and mosaicism of SNV/InDel. Mutations in some genes cannot be detected due to technical reasons including local sequence characteristics or the presence of closely related pseudogenes.

Turn Around Time (TAT): 20 calendar days (Trio), 28 calendar days (Proband only).

Specimen requirement: Please contact our lab at (852) 3505 1557.