Preprint identifies genomic regions with excess reciprocal recombination in autism spectrum disorder families

A preprint posted on bioRxiv describes new statistical methods for detecting genomic regions enriched for reciprocal recombination in the context of autism spectrum disorder (ASD), with application to two family-based datasets including the Simons Simplex Collection.

The biological rationale rests on a recognised feature of meiotic recombination: in some genomic regions, recombination rates are very low and variants remain in high linkage disequilibrium over long timescales. The authors propose that co-adapted haplotypes can accumulate in such regions, and that reciprocal recombination events separating these co-adapted variants may generate novel, deleterious haplotype combinations. This represents a distinct mechanism from the better-characterised de novo single-nucleotide variants and copy-number variants typically sought in ASD genetic studies.

The study develops two complementary statistical approaches tailored to different family-based study designs and applies them to identify candidate regions in ASD. The work is methodological as well as empirical, offering tools that could be applied to other neurodevelopmental and complex trait datasets.

As a preprint, the findings have not yet undergone peer review and should be treated as preliminary. The study is likely to be of primary interest to researchers in statistical genetics, neurodevelopmental genomics, and those working on the genetic architecture of ASD beyond conventional variant discovery.