Pangenome reconstruction in rats enhances genotype-phenotype mapping and variant discovery

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F25%3A00617646" target="_blank" >RIV/67985823:_____/25:00617646 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.isci.2025.111835" target="_blank" >https://doi.org/10.1016/j.isci.2025.111835</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.isci.2025.111835" target="_blank" >10.1016/j.isci.2025.111835</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pangenome reconstruction in rats enhances genotype-phenotype mapping and variant discovery

Popis výsledku v původním jazyce

The HXB/BXH family of recombinant inbred rat strains is a unique genetic resource that has been extensively phenotyped over 25 years, resulting in a vast dataset of quantitative molecular and physiological phenotypes. We built a pangenome graph from 10x Genomics Linked-Read data for 31 recombinant inbred rats to study genetic variation and association mapping. The pangenome includes 0.2Gb of sequence that is not present the reference mRatBN7.2, confirming the capture of substantial additional variation. We validated variants in challenging regions, including complex structural variants resolving into multiple haplotypes. Phenome-wide association analysis of validated SNPs uncovered variants associated with glucose/insulin levels and hippocampal gene expression. We propose an interaction between Pirl1l1, chromogranin expression, TNF-α levels, and insulin regulation. This study demonstrates the utility of linked-read pangenomes for comprehensive variant detection and mapping phenotypic diversity in a widely used rat genetic reference panel.

Název v anglickém jazyce

Pangenome reconstruction in rats enhances genotype-phenotype mapping and variant discovery

Popis výsledku anglicky

The HXB/BXH family of recombinant inbred rat strains is a unique genetic resource that has been extensively phenotyped over 25 years, resulting in a vast dataset of quantitative molecular and physiological phenotypes. We built a pangenome graph from 10x Genomics Linked-Read data for 31 recombinant inbred rats to study genetic variation and association mapping. The pangenome includes 0.2Gb of sequence that is not present the reference mRatBN7.2, confirming the capture of substantial additional variation. We validated variants in challenging regions, including complex structural variants resolving into multiple haplotypes. Phenome-wide association analysis of validated SNPs uncovered variants associated with glucose/insulin levels and hippocampal gene expression. We propose an interaction between Pirl1l1, chromogranin expression, TNF-α levels, and insulin regulation. This study demonstrates the utility of linked-read pangenomes for comprehensive variant detection and mapping phenotypic diversity in a widely used rat genetic reference panel.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

iScience

ISSN

2589-0042

e-ISSN

2589-0042

Svazek periodika

28

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

111835

Kód UT WoS článku

001449314500001

EID výsledku v databázi Scopus

2-s2.0-85217644363