TY - JOUR
T1 - The effect of developmental variation on expression QTLs in a multi parental C. elegans population
AU - van Eijnatten, A.L.
AU - Sterken, M.G.
AU - Kammenga, J.E.
AU - Nijveen, H.
AU - Snoek, B.L.
PY - 2024/2
Y1 - 2024/2
N2 - Regulation of gene expression plays a crucial role in developmental processes and adaptation to changing environments. eQTL mapping is a technique used to study the genetic regulation of gene expression using the transcriptomes of recombinant inbred lines. Typically, the age of the inbred lines at the time of RNA sampling is carefully controlled. This is necessary because the developmental process causes changes in gene expression, complicating the interpretation of eQTL mapping experiments. However, due to genetics and variation in ambient micro-environments, organisms can differ in their “developmental age”, even if they are of the same chronological age. As a result, eQTL patterns are affected by developmental variation in gene expression. The model organism C. elegans is particularly suited for studying the effect of developmental variation on eQTL mapping patterns. In a span of days, C. elegans transitions from embryo through four larval stages to adult while undergoing massive changes to its transcriptome. Here we use C. elegans to investigate the effect of developmental age variation on eQTL patterns and present a normalization procedure. We used dynamical eQTL mapping, which includes the developmental age as a co-factor, to separate the variation in development from genotypic variation and explain variation in gene expression levels. We compare classical single marker eQTL mapping and dynamical eQTL mapping using RNA-seq data of ∼200 multi-parental recombinant inbred lines of C. elegans. The results show i) that many eQTLs are caused by developmental variation, ii) most trans-bands are developmental QTLs and iii) dynamical eQTL mapping detects additional eQTLs not found with classical eQTL mapping. We recommend that correction for variation in developmental age should be strongly considered in eQTL mapping studies given the large impact of processes like development on the transcriptome.
AB - Regulation of gene expression plays a crucial role in developmental processes and adaptation to changing environments. eQTL mapping is a technique used to study the genetic regulation of gene expression using the transcriptomes of recombinant inbred lines. Typically, the age of the inbred lines at the time of RNA sampling is carefully controlled. This is necessary because the developmental process causes changes in gene expression, complicating the interpretation of eQTL mapping experiments. However, due to genetics and variation in ambient micro-environments, organisms can differ in their “developmental age”, even if they are of the same chronological age. As a result, eQTL patterns are affected by developmental variation in gene expression. The model organism C. elegans is particularly suited for studying the effect of developmental variation on eQTL mapping patterns. In a span of days, C. elegans transitions from embryo through four larval stages to adult while undergoing massive changes to its transcriptome. Here we use C. elegans to investigate the effect of developmental age variation on eQTL patterns and present a normalization procedure. We used dynamical eQTL mapping, which includes the developmental age as a co-factor, to separate the variation in development from genotypic variation and explain variation in gene expression levels. We compare classical single marker eQTL mapping and dynamical eQTL mapping using RNA-seq data of ∼200 multi-parental recombinant inbred lines of C. elegans. The results show i) that many eQTLs are caused by developmental variation, ii) most trans-bands are developmental QTLs and iii) dynamical eQTL mapping detects additional eQTLs not found with classical eQTL mapping. We recommend that correction for variation in developmental age should be strongly considered in eQTL mapping studies given the large impact of processes like development on the transcriptome.
U2 - 10.1093/g3journal/jkad273
DO - 10.1093/g3journal/jkad273
M3 - Article
SN - 2160-1836
JO - G3 : Genes Genomes Genetics
JF - G3 : Genes Genomes Genetics
M1 - jkad273
ER -