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Combined QTL and selective sweep mappings with coding SNP annotation and cis-eQTL analysis revealed PARK2 and JAG2 as new candidate genes for adiposity regulation.

Roux PF, Boitard S, Blum Y, Parks B, Montagner A, Mouisel E, Djari A, Esquerré D, Désert C, Boutin M, Leroux S, Lecerf F, Le Bihan-Duval E, Klopp C, Servin B, Pitel F, Duclos MJ, Guillou H, Lusis AJ, Demeure O, Lagarrigue S - G3 (Bethesda) (2015)

Bottom Line: Using new haplotype-based statistics exploiting the very high SNP density generated through whole-genome resequencing, we found 129 significant selective sweeps.We then focused on two of these QTL/sweeps.This study shows for the first time the interest of combining selective sweeps mapping, coding SNP annotation and cis-eQTL analyses for identifying causative genes for a complex trait, in the context of divergent lines selected for this specific trait.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1348 Pegase, Saint-Gilles, 35590, France Agrocampus Ouest, UMR1348 Pegase, Rennes, 35000, France Université Européenne de Bretagne, France.

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Expression characterizations of JAG2 in chicken. (A) Expression pattern of JAG2 in various tissues quantified using RT-qPCR. Results are given as expression fold change relative to the liver, which exhibited the lowest level of expression. (B) Comparison of JAG2 mRNA level in the fat line (FL, n = 12) and the lean line (LL, n = 12) in the liver and the white adipose tissue (WAT). Results are expressed as the expression ratio relatively to the LL ± SEM.
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fig3: Expression characterizations of JAG2 in chicken. (A) Expression pattern of JAG2 in various tissues quantified using RT-qPCR. Results are given as expression fold change relative to the liver, which exhibited the lowest level of expression. (B) Comparison of JAG2 mRNA level in the fat line (FL, n = 12) and the lean line (LL, n = 12) in the liver and the white adipose tissue (WAT). Results are expressed as the expression ratio relatively to the LL ± SEM.

Mentions: The AF5 QTL was of great interest because it included a single sweep, with hapFLK statistics values clearly exceeding those observed in the rest of the QTL (Figure 2). This very short sweep, measuring 1.3 kb and termed AF5, contained only a portion of the gene JAG2 (introns 17 to 19 and associated exons) (Figure S2). We did not find any indel or nonsynonymous SNPs suggesting the existence of causal polymorphism acting on the expression of this gene. Because liver and adipose tissue are major actors in lipid metabolism, we therefore focused on those tissues. We did not observe any significant differential expression between FL and LL in liver and adipose tissue (Figure 3B). We can hypothesize that JAG2 expression could be regulated in cis in other tissues to influence obesity in chicken because JAG2 is expressed in many tissues (Figure 3A), or that the age of birds we analyzed is irrelevant if there is any impact of developmental state on JAG2 expression. Nevertheless, because JAG2 is the only gene located in the sweep and colocalized with AF5 QTL, it is still a strong positional candidate gene for adiposity regulation.


Combined QTL and selective sweep mappings with coding SNP annotation and cis-eQTL analysis revealed PARK2 and JAG2 as new candidate genes for adiposity regulation.

Roux PF, Boitard S, Blum Y, Parks B, Montagner A, Mouisel E, Djari A, Esquerré D, Désert C, Boutin M, Leroux S, Lecerf F, Le Bihan-Duval E, Klopp C, Servin B, Pitel F, Duclos MJ, Guillou H, Lusis AJ, Demeure O, Lagarrigue S - G3 (Bethesda) (2015)

Expression characterizations of JAG2 in chicken. (A) Expression pattern of JAG2 in various tissues quantified using RT-qPCR. Results are given as expression fold change relative to the liver, which exhibited the lowest level of expression. (B) Comparison of JAG2 mRNA level in the fat line (FL, n = 12) and the lean line (LL, n = 12) in the liver and the white adipose tissue (WAT). Results are expressed as the expression ratio relatively to the LL ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390568&req=5

fig3: Expression characterizations of JAG2 in chicken. (A) Expression pattern of JAG2 in various tissues quantified using RT-qPCR. Results are given as expression fold change relative to the liver, which exhibited the lowest level of expression. (B) Comparison of JAG2 mRNA level in the fat line (FL, n = 12) and the lean line (LL, n = 12) in the liver and the white adipose tissue (WAT). Results are expressed as the expression ratio relatively to the LL ± SEM.
Mentions: The AF5 QTL was of great interest because it included a single sweep, with hapFLK statistics values clearly exceeding those observed in the rest of the QTL (Figure 2). This very short sweep, measuring 1.3 kb and termed AF5, contained only a portion of the gene JAG2 (introns 17 to 19 and associated exons) (Figure S2). We did not find any indel or nonsynonymous SNPs suggesting the existence of causal polymorphism acting on the expression of this gene. Because liver and adipose tissue are major actors in lipid metabolism, we therefore focused on those tissues. We did not observe any significant differential expression between FL and LL in liver and adipose tissue (Figure 3B). We can hypothesize that JAG2 expression could be regulated in cis in other tissues to influence obesity in chicken because JAG2 is expressed in many tissues (Figure 3A), or that the age of birds we analyzed is irrelevant if there is any impact of developmental state on JAG2 expression. Nevertheless, because JAG2 is the only gene located in the sweep and colocalized with AF5 QTL, it is still a strong positional candidate gene for adiposity regulation.

Bottom Line: Using new haplotype-based statistics exploiting the very high SNP density generated through whole-genome resequencing, we found 129 significant selective sweeps.We then focused on two of these QTL/sweeps.This study shows for the first time the interest of combining selective sweeps mapping, coding SNP annotation and cis-eQTL analyses for identifying causative genes for a complex trait, in the context of divergent lines selected for this specific trait.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1348 Pegase, Saint-Gilles, 35590, France Agrocampus Ouest, UMR1348 Pegase, Rennes, 35000, France Université Européenne de Bretagne, France.

Show MeSH
Related in: MedlinePlus