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Meta-Analysis
. 2023 Jun 19;24(1):338.
doi: 10.1186/s12864-023-09438-7.

X-linked genes influence various complex traits in dairy cattle

Marie-Pierre Sanchez  1 , Clémentine Escouflaire  2 , Aurélia Baur  2 , Fiona Bottin  3 , Chris Hozé  2 , Mekki Boussaha  3 , Sébastien Fritz  2 , Aurélien Capitan  3 , Didier Boichard  3
Affiliations
Meta-Analysis

X-linked genes influence various complex traits in dairy cattle

Marie-Pierre Sanchez et al. BMC Genomics. .

Abstract

Background: The search for quantitative trait loci (QTL) affecting traits of interest in mammals is frequently limited to autosomes, with the X chromosome excluded because of its hemizygosity in males. This study aimed to assess the importance of the X chromosome in the genetic determinism of 11 complex traits related to milk production, milk composition, mastitis resistance, fertility, and stature in 236,496 cows from three major French dairy breeds (Holstein, Montbéliarde, and Normande) and three breeds of regional importance (Abondance, Tarentaise, and Vosgienne).

Results: Estimates of the proportions of heritability due to autosomes and X chromosome (h²X) were consistent among breeds. On average over the 11 traits, h²X=0.008 and the X chromosome explained ~ 3.5% of total genetic variance. GWAS was performed within-breed at the sequence level (~ 200,000 genetic variants) and then combined in a meta-analysis. QTL were identified for most breeds and traits analyzed, with the exception of Tarentaise and Vosgienne and two fertility traits. Overall, 3, 74, 59, and 71 QTL were identified in Abondance, Montbéliarde, Normande, and Holstein, respectively, and most were associated with the most-heritable traits (milk traits and stature). The meta-analyses, which assessed a total of 157 QTL for the different traits, highlighted new QTL and refined the positions of some QTL found in the within-breed analyses. Altogether, our analyses identified a number of functional candidate genes, with the most notable being GPC3, MBNL3, HS6ST2, and DMD for dairy traits; TMEM164, ACSL4, ENOX2, HTR2C, AMOT, and IRAK1 for udder health; MAMLD1 and COL4A6 for fertility; and NRK, ESX1, GPR50, GPC3, and GPC4 for stature.

Conclusions: This study demonstrates the importance of the X chromosome in the genetic determinism of complex traits in dairy cattle and highlights new functional candidate genes and variants for these traits. These results could potentially be extended to other species as many X-linked genes are shared among mammals.

Keywords: Dairy cattle; GWAS; Meta-analyses; X chromosome.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Iterative procedure for defining QTL and their confidence intervals
Fig. 2
Fig. 2
UpSet diagrams for variants within the confidence intervals of QTL detected in within-breed and meta-analyses of association. (a) milk yield (MY), (b) fat yield (FY), (c) protein yield (PY), (d) fat content (FC), (e) protein content (PC), (f) somatic cell score (SCS), (g) interval between calving and first insemination (ICFI), and (h) stature (STAT).
Fig. 3
Fig. 3
Results of within-breed and meta-analyses of the X chromosome for protein content (PC): Manhattan plot for the entire chromosome and LocusZoom graph for the QTL with the most significant effects. Within-breed association analyses in Abondance, Montbéliarde, Normande, and Holstein cows (Manhattan plot in blue); fixed effects meta-analyses (Manhattan plot in gray, variants with effects in the same direction in all within-breed analyses are highlighted in green); and corresponding LocusZoom graphs for the 20-Mb interval centered around the variant with the most significant effect
Fig. 4
Fig. 4
Results of within-breed and meta-analyses of the X chromosome for somatic cell score (SCS): Manhattan plot for the entire chromosome and LocusZoom graph for the QTL with the most significant effects. Within-breed association analyses in Montbéliarde, Normande, and Holstein cows (Manhattan plot in blue); fixed effects meta-analyses (Manhattan plot in gray, variants with effects in the same direction in all within-breed analyses are highlighted in green); and corresponding LocusZoom graphs for the 20-Mb interval centered around the variant with the most significant effect
Fig. 5
Fig. 5
Results of within-breed and meta-analyses of the X chromosome for interval between calving and first insemination (ICFI): Manhattan plot for the entire chromosome and LocusZoom graph for the QTL with the most significant effects. Within-breed association analyses in Montbéliarde, Normande, and Holstein cows (Manhattan plot in blue); fixed effects meta-analyses (Manhattan plot in gray, variants with effects in the same direction in all within-breed analyses are highlighted in green); and corresponding LocusZoom graphs for the 20-Mb interval centered around the variant with the most significant effect
Fig. 6
Fig. 6
Results of within-breed and meta-analyses of the X chromosome for stature (STAT): Manhattan plot for the entire chromosome and LocusZoom graph for the QTL with the most significant effects in meta-analyses. Within-breed association analyses in Montbéliarde, Normande, and Holstein cows (Manhattan plot in blue); fixed effects meta-analyses (Manhattan plot in gray, variants with effects in the same direction in all within-breed analyses are highlighted in green); and corresponding LocusZoom graphs for the 20-Mb interval centered around the variant with the most significant effect in both the within-breed Montbéliarde analysis and meta-analysis
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