Lp(a) and KIV-2

KILDA

Lipoprotein(a) is a largely genetically fixed risk factor for cardiovascular disease. Its level depends strongly on the copy number of the KIV-2 repeat in the LPA gene. Genome estimates this copy number from sequence data.

LPA GENE · KIV-2 COPY NUMBER n × KIV-2 · variable 5-40 copies KIV-1 KIV-2 KIV-3 … KIV-10 KV protease Lp(a) KIV-2 copies → Few copies short isoform, high Lp(a) Many copies long isoform, low Lp(a)

Why copy number matters

The KIV-2 repeats lengthen or shorten apolipoprotein(a). Short isoforms are secreted more efficiently and go along with higher plasma levels. Because the highly repetitive region is hard to access for short-read sequencing, it needs dedicated methods rather than simple alignment counting.

How Genome analyses

Genome uses KILDA, which estimates the KIV-2 length via k-mer counting directly from FASTQ reads, without relying on a full alignment of the repetitive region. The result appears as technical evidence in the medical genomics report, separated from interpretation and limits.

What Genome measures. The estimated KIV-2 copy number as a proxy for the LPA isoform size, derived from a k-mer-based analysis of the reads.

Related topics

Structural variantsDisease associations

Sources

  1. 1Kronenberg et al., 2022 Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal 43:3925–3946. doi.org/10.1093/eurheartj/ehac361
  2. 2Coassin & Kronenberg, 2022 Lipoprotein(a) beyond the kringle IV repeat polymorphism: from genotype to phenotype. Atherosclerosis 349:17–35. doi.org/10.1016/j.atherosclerosis.2022.04.003