Identification of chromosomal abnormalities in miscarriages using single-nucleotide polymorphism arrays

Area of Science:

• Reproductive genetics
• Human genetics
• Genomic medicine

Background:

• Chromosome abnormalities are a significant factor contributing to miscarriage.
• Understanding the genetic basis of miscarriage is crucial for reproductive health.
• High-throughput technologies offer advanced methods for chromosomal analysis.

Purpose of the Study:

• To conduct a detailed chromosomal study of miscarriages using high-throughput technologies.
• To identify the types and frequencies of chromosomal abnormalities in a cohort of miscarriages.
• To investigate the role of various chromosomal aberrations in pregnancy loss.

Main Methods:

• Analysis of 564 miscarriages using high-throughput single-nucleotide polymorphism (SNP) array.
• Detection of chromosomal abnormalities including triploidy, trisomy, monosomy, uniparental disomy, and deletions/duplications.
• Categorization of variants into pathogenic, variations of unknown significance (VOUS), and no clinically relevant variants.

Main Results:

• Chromosomal abnormalities were detected in 336 (59.6%) of the 564 miscarriages.
• Pathogenic variants were identified in 325 (57.6%) cases, with trisomy (225 cases) and monosomy X (39 cases) being most common.
• Partial chromosomal deletions/duplications were found in 32 miscarriages, while 228 (40.4%) showed no clinically relevant chromosomal variants.

Conclusions:

• Trisomy and monosomy X are confirmed as leading causes of miscarriage.
• Chromosomal deletions and duplications also contribute to miscarriage.
• The significant proportion of miscarriages with no detected variants suggests the involvement of other genetic factors, potentially single gene mutations requiring further investigation via high-throughput sequencing.