Genome-wide recombination map construction from single individuals using linked-read sequencing

Andreea Dréau,Vrinda Venu,Elena Avdievich,Ludmila Gaspar,Felicity C Jones

doi:10.1038/s41467-019-12210-9

Andreea Dréau, Vrinda Venu + Show 3 more

Open Access

https://doi.org/10.1038/s41467-019-12210-9

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Abstract

Meiotic recombination rates vary across the genome, often involving localized crossover hotspots and coldspots. Studying the molecular basis and mechanisms underlying this variation has been challenging due to the high cost and effort required to construct individualized genome-wide maps of recombination crossovers. Here we introduce a new method, called ReMIX, to detect crossovers from gamete DNA of a single individual using Illumina sequencing of 10X Genomics linked-read libraries. ReMIX reconstructs haplotypes and identifies the valuable rare molecules spanning crossover breakpoints, allowing quantification of the genomic location and intensity of meiotic recombination. Using a single mouse and stickleback fish, we demonstrate how ReMIX faithfully recovers recombination hotspots and landscapes that have previously been built using hundreds of offspring. ReMIX provides a high-resolution, high-throughput, and low-cost approach to quantify recombination variation across the genome, providing an exciting opportunity to study recombination among multiple individuals in diverse organisms.

Highlights

Meiotic recombination rates vary across the genome, often involving localized crossover hotspots and coldspots
We report the complete pipeline and results obtained by applying our method to an individual C57BL/6Ncrl × CAST/EiJ hybrid mouse and freshwater stickleback fish
HMW DNA (>40 kb) was extracted from purified sperm cells and somatic tissue of both mouse and fish individuals. 10X Genomics linked-read genomic libraries were prepared on a Chromium controller and the resulting linked-read libraries were sequenced on an Illumina HiSeq3000 sequencer

Summary

Introduction

Meiotic recombination rates vary across the genome, often involving localized crossover hotspots and coldspots. Excessive, or deficient recombination can cause inviable gametes and developmental abnormalities[2,3] For these reasons the number of crossovers and their genomic locations are thought to be tightly regulated and highly constrained[4]. Despite this core functional constraint, recent studies have revealed remarkable variation in recombination at multiple different scales (between and along chromosomes, among individuals, sexes, populations, and species/taxa)[5,6,7,8,9,10,11,12]. Depending on the evolutionary context, recombination may be beneficial if it breaks down linkage between deleterious and beneficial alleles (known as the Hill–Robertson effect15,16), or deleterious if it breaks linkage between two adaptive alleles[17]

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