Fine mapping and replication of QTL in outbred chicken advanced intercross lines.
BACKGROUND
Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F(2) populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F(2) animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.


METHODS
We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F(2) population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.


RESULTS
Five of the nine QTL detected with the original F(2) population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.


CONCLUSIONS
Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. francois.besnier@imr.no
Francois
F
Besnier
Per
P
Wahlberg
Lars
L
Rönnegård
Weronica
W
Ek
Leif
L
Andersson
Paul B
PB
Siegel
Orjan
O
Carlborg
D000818:Animals; D021461:Animals, Outbred Strains; D002645:Chickens / Q000235:genetics*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005838:Genotype; D015810:Linkage Disequilibrium / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
Theor Appl Genet. 1989 Nov;78(5):613-8
24225819
BMC Genet. 2009 Sep 17;10:57
19761594
Am J Hum Genet. 1997 Sep;61(3):748-60
9326339
Physiol Genomics. 2006 Apr 13;25(2):216-23
16390876
Genetics. 2001 Sep;159(1):413-22
11560915
Genes Immun. 2007 Jun;8(4):296-301
17361202
Cytogenet Genome Res. 2007;117(1-4):22-9
17675841
BMC Genet. 2007 Jan 08;8:1
17210073
Genetics. 2000 May;155(1):421-30
10790414
PLoS Genet. 2010 Nov 04;6(11):e1001188
21079680
Genetics. 1995 Nov;141(3):1199-207
8582624
Genet Res. 2005 Oct;86(2):115-25
16356285
Genetics. 2009 Jun;182(2):541-54
19363126
Mamm Genome. 2006 Jun;17(6):584-97
16783640
Genetics. 2008 Apr;178(4):2315-26
18430952
Poult Sci. 1996 Oct;75(10):1168-79
8893291
Genetics. 1993 Jul;134(3):943-51
8349116
Nat Genet. 2002 Jan;30(1):97-101
11731797
Genome Res. 2009 Mar;19(3):510-9
19088305
Nat Genet. 2006 Apr;38(4):418-20
16532011
Am J Hum Genet. 1990 Dec;47(6):957-67
2239972
Genetics. 2006 Mar;172(3):1783-97
16361245
Nature. 2004 Dec 9;432(7018):717-22
15592405
Theor Appl Genet. 1992 Dec;85(4):480-8
24197463
Heredity (Edinb). 1992 Oct;69(4):315-24
16718932
BMC Genomics. 2009 May 27;10:248
19473501
Genet Sel Evol. 2001 Sep-Oct;33(5):453-71
11712969
Science. 1994 Mar 25;263(5154):1771-4
8134840