FWF-funded project: Multi-ancestry LPA KIV-2 haplotype analysis and imputation
About
The KIV-2 copy number variation (CNV) region constitutes up to 70% of the LPA gene, yet its highly repetitive structure has long hindered comprehensive genomic analysis. As a result, this region remains largely absent from current genome variation databases, SNP imputation pipelines, and genome-wide association studies (GWAS). Nevertheless, previous work by our group and others has demonstrated that this complex region harbors important genetic variants that strongly influence lipoprotein(a) [Lp(a)] plasma concentrations and contribute to cardiovascular risk.
This project, funded by the Austrian Science Fund (FWF; Grant DOI: 10.55776/PAT5152823), aims to characterize genetic variation and haplotype structures within the KIV-2 region across diverse ancestries. To achieve this, we will analyze samples from the 1000 Genomes Project alongside local European cohorts using a newly developed high-precision nanopore sequencing approach. This method incorporates unique molecular identifiers (UMIs) to enable single-molecule error correction and highly accurate variant detection.
The project has four main objectives:
- Characterize haplotypic diversity within the KIV-2 region in the samples from the 1000 Genomes Project and in local European individuals with known KIV-2 copy numbers.
- Assess the concordance between KIV-2 copy number and KIV-2 haplotype number, and identify isoform-specific haplotypes.
- Develop and evaluate rapid de novo assembly strategies for biallelic KIV-2 CNVs using overlapping amplicons.
- Investigate opportunities for KIV-2 SNP imputation and develop a dedicated SNP imputation tool.
Team
Lab rotation student
Bachelor Student (graduated)
Publications originated from this project
No publication found in publications.csv file for PMID 41923360
Coassin S: Recent advances in understanding the spectrum of genetic determinants of lipoprotein(a) levels. Curr. Opin. Lipidol. 37:65-72, 2026. PMID: 41655037 Review
Amstler S, Streiter G, Pfurtscheller C, Forer L, Di Maio S, Weissensteiner H, Paulweber B, Schönherr S, Kronenberg F, Coassin S: Nanopore sequencing with unique molecular identifiers enables accurate mutation analysis and haplotyping in the complex lipoprotein(a) KIV-2 VNTR. Genome Med. 16:117, 2024. PMID: 39380090 Journal Article
Further stats on the outcomes of this project can be found in the FWF Research Radar.