In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

被引：13

作者：

Hadsell, Darryl L. ^{[1
,2
]}

Hadsell, Louise A. ^{[1
]}

Olea, Walter ^{[1
]}

Rijnkels, Monique ^{[3
]}

Creighton, Chad J. ^{[4
]}

Smyth, Ian ^{[5
,6
]}

Short, Kieran M. ^{[6
]}

Cox, Liza L. ^{[7
,8
]}

Cox, Timothy C. ^{[7
,8
]}

机构：

[1] Baylor Coll Med, Dept Pediat, USDA ARS Childrens Nutr Res Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[3] Texas A&M Univ, Dept Vet Integrat Biosci, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA

[4] Baylor Coll Med, Div Biostat, Dept Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[5] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3800, Australia

[6] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[7] Univ Washington, Dept Pediat, Sch Med, Seattle, WA 98101 USA

[8] Seattle Childrens Res Inst, Ctr Dev Biol & Regenerat Med, Seattle, WA 98101 USA

来源：

MAMMALIAN GENOME | 2015年 / 26卷 / 1-2期

基金：

澳大利亚研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GLAND DEVELOPMENT; BRANCHING MORPHOGENESIS; GENE-EXPRESSION; MICE LACKING; TARGET SITE; STRAINS; TBX3; IDENTIFICATION; MUTATIONS;

D O I：

10.1007/s00335-014-9551-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genetic background plays a dominant role in mammary gland development and breast cancer (BrCa). Despite this, the role of genetics is only partially understood. This study used strain-dependent variation in an inbred mouse mapping panel, to identify quantitative trait loci (QTL) underlying structural variation in mammary ductal development, and determined if these QTL correlated with genomic intervals conferring BrCa susceptibility in humans. For about half of the traits, developmental variation among the complete set of strains in this study was greater (P < 0.05) than that of previously studied strains, or strains in current common use for mammary gland biology. Correlations were also detected with previously reported variation in mammary tumor latency and metastasis. In-silico genome-wide association identified 20 mammary development QTL (Mdq). Of these, five were syntenic with previously reported human BrCa loci. The most significant (P = 1 x 10(-11)) association of the study was on MMU6 and contained the genes Plxna4, Plxna4os1, and Chchd3. On MMU5, a QTL was detected (P = 8 x 10(-7)) that was syntenic to a human BrCa locus on h12q24.5 containing the genes Tbx3 and Tbx5. Intersection of linked SNP (r(2) > 0.8) with genomic and epigenomic features, and intersection of candidate genes with gene expression and survival data from human BrCa highlighted several for further study. These results support the conclusion that mammary tumorigenesis and normal ductal development are influenced by common genetic factors and that further studies of genetically diverse mice can improve our understanding of BrCa in humans.

引用

页码：57 / 79

页数：23

共 114 条

[11]

Bean SL, 2000, JAX NOTES, V480, P1

[12]

Betts MJ, 2003, BIOINFORMATICS GENET

[13] PolymiRTS Database 3.0: linking polymorphisms in microRNAs and their target sites with human diseases and biological pathways [J].

Bhattacharya, Anindya ;

Ziebarth, Jesse D. ;

Cui, Yan .

NUCLEIC ACIDS RESEARCH, 2014, 42 (D1) :D86-D91

[14] Annotation of functional variation in personal genomes using RegulomeDB [J].

Boyle, Alan P. ;

Hong, Eurie L. ;

Hariharan, Manoj ;

Cheng, Yong ;

Schaub, Marc A. ;

Kasowski, Maya ;

Karczewski, Konrad J. ;

Park, Julie ;

Hitz, Benjamin C. ;

Weng, Shuai ;

Cherry, J. Michael ;

Snyder, Michael .

GENOME RESEARCH, 2012, 22 (09) :1790-1797

[15] Identification of fifteen novel germline variants in the BRCA1 3′UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site [J].

Brewster, Brooke L. ;

Rossiello, Francesca ;

French, Juliet D. ;

Edwards, Stacey L. ;

Wong, Ming ;

Wronski, Ania ;

Whiley, Phillip ;

Waddell, Nic ;

Chen, Xiaowei ;

Bove, Betsy ;

Hopper, John L. ;

John, Esther M. ;

Andrulis, Irene ;

Daly, Mary ;

Volorio, Sara ;

Bernard, Loris ;

Peissel, Bernard ;

Manoukian, Siranoush ;

Barile, Monica ;

Pizzamiglio, Sara ;

Verderio, Paolo ;

Spurdle, Amanda B. ;

Radice, Paolo ;

Godwin, Andrew K. ;

Southey, Melissa C. ;

Brown, Melissa A. ;

Peterlongo, Paolo .

HUMAN MUTATION, 2012, 33 (12) :1665-1675

[16] Fine-Scale Maps of Recombination Rates and Hotspots in the Mouse Genome [J].

Brunschwig, Hadassa ;

Levi, Liat ;

Ben-David, Eyal ;

Williams, Robert W. ;

Yakir, Benjamin ;

Shifman, Sagiv .

GENETICS, 2012, 191 (03) :757-U169

[17] Defining the Molecular Character of the Developing and Adult Kidney Podocyte [J].

Brunskill, Eric W. ;

Georgas, Kylie ;

Rumballe, Bree ;

Little, Melissa H. ;

Potter, S. Steven .

PLOS ONE, 2011, 6 (09)

[18] LOCALIZATION AND QUANTIFICATION OF WNT-2 GENE-EXPRESSION IN MOUSE MAMMARY DEVELOPMENT [J].

BUHLER, TA ;

DALE, TC ;

KIEBACK, C ;

HUMPHREYS, RC ;

ROSEN, JM .

DEVELOPMENTAL BIOLOGY, 1993, 155 (01) :87-96

[19] An experimental assessment of in silico haplotype association mapping in laboratory mice [J].

Burgess-Herbert, Sarah L. ;

Tsaih, Shirng-Wern ;

Stylianou, Ioannis M. ;

Walsh, Kenneth ;

Cox, Allison J. ;

Paigen, Beverly .

BMC GENETICS, 2009, 10

[20] Genetic up-regulation and overexpression of PLEKHA7 differentiates invasive lobular carcinomas from invasive ductal carcinomas [J].

Castellana, Barbara ;

Escuin, Daniel ;

Perez-Olabarria, Maitane ;

Vazquez, Tania ;

Munoz, Josefina ;

Peiro, Gloria ;

Barnadas, Agusti ;

Lerma, Enrique .

HUMAN PATHOLOGY, 2012, 43 (11) :1902-1909

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