Personalized genome structure via single gamete sequencing

Abstract

Genetic maps have been fundamental to building our understanding of disease genetics and evolutionary processes. The gametes of an individual contain all of the information required to perform a de novo chromosome-scale assembly of an individual’s genome, which historically has been performed with populations and pedigrees. Here, we discuss how single-cell gamete sequencing offers the potential to merge the advantages of short-read sequencing with the ability to build personalized genetic maps and open up an entirely new space in personalized genetics.

sgcocaller and comapr: personalised haplotype assembly and comparative crossover map analysis using single-gamete sequencing data

“…With the advancement of single-cell DNA sequencing technologies that generate larger-scale and higher-quality datasets, our software serves as a complete toolkit as the first step to inspect the single gamete data of an individual for understanding individual-level variations in meiotic crossovers [9].…”

“…The multiple release formats of sgcocaller enable it to be more accessible to the community. Advances in single-cell DNA sequencing technologies that generate larger-scale and higher-quality datasets enable exciting opportunities for research using personalised meiotic crossover landscapes (11). Abnormal meiotic crossovers are often associated with infertility (5).…”

“…Meiotic crossovers are also required for accurate chromosome segregation [1] and reduced crossover rates are linked to increased risk for trisomy 21 [2, 3]. Past studies have shown that meiotic crossover rates and distributions vary greatly among species, sexes and even individuals [4, 5, 6, 7, 8, 9]. Variation in genetic factors, such as PRDM9 , changes the distribution of crossover hotpots in human and mouse [10, 11, 6, 4].…”

“…It has also been shown that meiotic crossovers vary among sexes and crossover hotspots can be sex-specific (7,10,19). Single-cell DNA sequencing of gametes collected from an individual can be used to construct personalised meiotic crossover distributions (9,11). The scalability of modern single-cell assays, especially droplet-based platforms, has made it possible to profile thousands of sperm cells per individual in one experiment (9).…”

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

“…This can generate antibiotic resistance, with significant relevance in different research areas [43]. Additionally, another of the most interesting applications of genome sequencing is personalized medicine, like sequencing single gametes [44,45]. Nucleic acids can also be used to store any kind of information in a compact and efficient way which can be retrieved by sequencing and decoding [46].…”