The genome architecture of the collaborative cross mouse genetic reference population

Fuad A. Iraqi, Mustafa Mahajne, Yasser Salaymah, Hani Sandovski, Hanna Tayem, Karin Vered, Lois Balmer, Michael Hall, Glynn Manship, Grant Morahan, Ken Pettit, Jeremy Scholten, Kathryn Tweedie, Andrew Wallace, Lakshini Weerasekera, James Cleak, Caroline Durrant, Leo Goodstadt, Richard Mott, Binnaz Yalcin & 110 others David L. Aylor, Ralph S. Baric, Timothy A. Bell, Katharine M. Bendt, Jennifer Brennan, Jackie D. Brooks, Ryan J. Buus, James J. Crowley, John D. Calaway, Mark E. Calaway, Agnieszka Cholka, David B. Darr, John P. Didion, Amy Dorman, Eric T. Everett, Martin T. Ferris, Wendy Foulds Mathes, Chen Ping Fu, Terry J. Gooch, Summer G. Goodson, Lisa E. Gralinski, Stephanie D. Hansen, Mark T. Heise, Jane Hoel, Kunjie Hua, Mayanga C. Kapita, Seunggeun Lee, Alan B. Lenarcic, Eric Yi Liu, Hedi Liu, Leonard McMillan, Terry R. Magnuson, Kenneth F. Manly, Darla R. Miller, Deborah A. O'Brien, Fanny Odet, Isa Kemal Pakatci, Wenqi Pan, Fernando Pardo Manuel de Villena, Charles M. Perou, Daniel Pomp, Corey R. Quackenbush, Nashiya N. Robinson, Norman E. Sharpless, Ginger D. Shaw, Jason S. Spence, Patrick F. Sullivan, Wei Sun, Lisa M. Tarantino, William Valdar, Jeremy Wang, Wei Wang, Catherine E. Welsh, Alan Whitmore, Tim Wiltshire, Fred A. Wright, Yuying Xie, Zaining Yun, Vasyl Zhabotynsky, Zhaojun Zhang, Fei Zou, Christine Powell, Jill Steigerwalt, David W. Threadgill, Elissa J. Chesler, Gary A. Churchill, Daniel M. Gatti, Ron Korstanje, Karen L. Svenson, Francis S. Collins, Nigel Crawford, Kent Hunter, N. Samir, P. Kelada, Bailey C.E. Peck, Karlyne Reilly, Urraca Tavarez, Daniel Bottomly, Robert Hitzeman, Shannon K. Mcweeney, Jeffrey Frelinger, Harsha Krovi, Jason Phillippi, Richard A. Spritz, Lauri Aicher, Michael Katze, Elizabeth Rosenzweig, Ariel Shusterman, Aysar Nashef, Ervin I. Weiss, Yael Houri-Haddad, Morris Soller, Robert Williams, Klaus Schughart, Hyuna Yang, John E. French, Andrew K. Benson, Jaehyoung Kim, Ryan Legge, Soo Jen Low, Fangrui Ma, Ines Martinez, Jens Walter, Karl W. Broman, Benedikt Hallgrimsson, Ophir Klein, George Weinstock, Wesley C. Warren, Yvana V. Yang, David Schwartz

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multi parental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.

Original languageEnglish (US)
Pages (from-to)389-401
Number of pages13
JournalGenetics
Volume190
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Genetic Crosses
Population Genetics
Genome
Breeding
Population
Haplotypes
Alleles
Western Australia
Chromosomes, Human, Pair 2
Inbreeding
Genetic Structures
Linkage Disequilibrium
X Chromosome
Single Nucleotide Polymorphism
Mammals
Genotype

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Iraqi, F. A., Mahajne, M., Salaymah, Y., Sandovski, H., Tayem, H., Vered, K., ... Schwartz, D. (2012). The genome architecture of the collaborative cross mouse genetic reference population. Genetics, 190(2), 389-401. https://doi.org/10.1534/genetics.111.132639

The genome architecture of the collaborative cross mouse genetic reference population. / Iraqi, Fuad A.; Mahajne, Mustafa; Salaymah, Yasser; Sandovski, Hani; Tayem, Hanna; Vered, Karin; Balmer, Lois; Hall, Michael; Manship, Glynn; Morahan, Grant; Pettit, Ken; Scholten, Jeremy; Tweedie, Kathryn; Wallace, Andrew; Weerasekera, Lakshini; Cleak, James; Durrant, Caroline; Goodstadt, Leo; Mott, Richard; Yalcin, Binnaz; Aylor, David L.; Baric, Ralph S.; Bell, Timothy A.; Bendt, Katharine M.; Brennan, Jennifer; Brooks, Jackie D.; Buus, Ryan J.; Crowley, James J.; Calaway, John D.; Calaway, Mark E.; Cholka, Agnieszka; Darr, David B.; Didion, John P.; Dorman, Amy; Everett, Eric T.; Ferris, Martin T.; Mathes, Wendy Foulds; Fu, Chen Ping; Gooch, Terry J.; Goodson, Summer G.; Gralinski, Lisa E.; Hansen, Stephanie D.; Heise, Mark T.; Hoel, Jane; Hua, Kunjie; Kapita, Mayanga C.; Lee, Seunggeun; Lenarcic, Alan B.; Liu, Eric Yi; Liu, Hedi; McMillan, Leonard; Magnuson, Terry R.; Manly, Kenneth F.; Miller, Darla R.; O'Brien, Deborah A.; Odet, Fanny; Pakatci, Isa Kemal; Pan, Wenqi; de Villena, Fernando Pardo Manuel; Perou, Charles M.; Pomp, Daniel; Quackenbush, Corey R.; Robinson, Nashiya N.; Sharpless, Norman E.; Shaw, Ginger D.; Spence, Jason S.; Sullivan, Patrick F.; Sun, Wei; Tarantino, Lisa M.; Valdar, William; Wang, Jeremy; Wang, Wei; Welsh, Catherine E.; Whitmore, Alan; Wiltshire, Tim; Wright, Fred A.; Xie, Yuying; Yun, Zaining; Zhabotynsky, Vasyl; Zhang, Zhaojun; Zou, Fei; Powell, Christine; Steigerwalt, Jill; Threadgill, David W.; Chesler, Elissa J.; Churchill, Gary A.; Gatti, Daniel M.; Korstanje, Ron; Svenson, Karen L.; Collins, Francis S.; Crawford, Nigel; Hunter, Kent; Samir, N.; Kelada, P.; Peck, Bailey C.E.; Reilly, Karlyne; Tavarez, Urraca; Bottomly, Daniel; Hitzeman, Robert; Mcweeney, Shannon K.; Frelinger, Jeffrey; Krovi, Harsha; Phillippi, Jason; Spritz, Richard A.; Aicher, Lauri; Katze, Michael; Rosenzweig, Elizabeth; Shusterman, Ariel; Nashef, Aysar; Weiss, Ervin I.; Houri-Haddad, Yael; Soller, Morris; Williams, Robert; Schughart, Klaus; Yang, Hyuna; French, John E.; Benson, Andrew K.; Kim, Jaehyoung; Legge, Ryan; Low, Soo Jen; Ma, Fangrui; Martinez, Ines; Walter, Jens; Broman, Karl W.; Hallgrimsson, Benedikt; Klein, Ophir; Weinstock, George; Warren, Wesley C.; Yang, Yvana V.; Schwartz, David.

In: Genetics, Vol. 190, No. 2, 01.02.2012, p. 389-401.

Research output: Contribution to journalArticle

Iraqi, FA, Mahajne, M, Salaymah, Y, Sandovski, H, Tayem, H, Vered, K, Balmer, L, Hall, M, Manship, G, Morahan, G, Pettit, K, Scholten, J, Tweedie, K, Wallace, A, Weerasekera, L, Cleak, J, Durrant, C, Goodstadt, L, Mott, R, Yalcin, B, Aylor, DL, Baric, RS, Bell, TA, Bendt, KM, Brennan, J, Brooks, JD, Buus, RJ, Crowley, JJ, Calaway, JD, Calaway, ME, Cholka, A, Darr, DB, Didion, JP, Dorman, A, Everett, ET, Ferris, MT, Mathes, WF, Fu, CP, Gooch, TJ, Goodson, SG, Gralinski, LE, Hansen, SD, Heise, MT, Hoel, J, Hua, K, Kapita, MC, Lee, S, Lenarcic, AB, Liu, EY, Liu, H, McMillan, L, Magnuson, TR, Manly, KF, Miller, DR, O'Brien, DA, Odet, F, Pakatci, IK, Pan, W, de Villena, FPM, Perou, CM, Pomp, D, Quackenbush, CR, Robinson, NN, Sharpless, NE, Shaw, GD, Spence, JS, Sullivan, PF, Sun, W, Tarantino, LM, Valdar, W, Wang, J, Wang, W, Welsh, CE, Whitmore, A, Wiltshire, T, Wright, FA, Xie, Y, Yun, Z, Zhabotynsky, V, Zhang, Z, Zou, F, Powell, C, Steigerwalt, J, Threadgill, DW, Chesler, EJ, Churchill, GA, Gatti, DM, Korstanje, R, Svenson, KL, Collins, FS, Crawford, N, Hunter, K, Samir, N, Kelada, P, Peck, BCE, Reilly, K, Tavarez, U, Bottomly, D, Hitzeman, R, Mcweeney, SK, Frelinger, J, Krovi, H, Phillippi, J, Spritz, RA, Aicher, L, Katze, M, Rosenzweig, E, Shusterman, A, Nashef, A, Weiss, EI, Houri-Haddad, Y, Soller, M, Williams, R, Schughart, K, Yang, H, French, JE, Benson, AK, Kim, J, Legge, R, Low, SJ, Ma, F, Martinez, I, Walter, J, Broman, KW, Hallgrimsson, B, Klein, O, Weinstock, G, Warren, WC, Yang, YV & Schwartz, D 2012, 'The genome architecture of the collaborative cross mouse genetic reference population', Genetics, vol. 190, no. 2, pp. 389-401. https://doi.org/10.1534/genetics.111.132639
Iraqi FA, Mahajne M, Salaymah Y, Sandovski H, Tayem H, Vered K et al. The genome architecture of the collaborative cross mouse genetic reference population. Genetics. 2012 Feb 1;190(2):389-401. https://doi.org/10.1534/genetics.111.132639
Iraqi, Fuad A. ; Mahajne, Mustafa ; Salaymah, Yasser ; Sandovski, Hani ; Tayem, Hanna ; Vered, Karin ; Balmer, Lois ; Hall, Michael ; Manship, Glynn ; Morahan, Grant ; Pettit, Ken ; Scholten, Jeremy ; Tweedie, Kathryn ; Wallace, Andrew ; Weerasekera, Lakshini ; Cleak, James ; Durrant, Caroline ; Goodstadt, Leo ; Mott, Richard ; Yalcin, Binnaz ; Aylor, David L. ; Baric, Ralph S. ; Bell, Timothy A. ; Bendt, Katharine M. ; Brennan, Jennifer ; Brooks, Jackie D. ; Buus, Ryan J. ; Crowley, James J. ; Calaway, John D. ; Calaway, Mark E. ; Cholka, Agnieszka ; Darr, David B. ; Didion, John P. ; Dorman, Amy ; Everett, Eric T. ; Ferris, Martin T. ; Mathes, Wendy Foulds ; Fu, Chen Ping ; Gooch, Terry J. ; Goodson, Summer G. ; Gralinski, Lisa E. ; Hansen, Stephanie D. ; Heise, Mark T. ; Hoel, Jane ; Hua, Kunjie ; Kapita, Mayanga C. ; Lee, Seunggeun ; Lenarcic, Alan B. ; Liu, Eric Yi ; Liu, Hedi ; McMillan, Leonard ; Magnuson, Terry R. ; Manly, Kenneth F. ; Miller, Darla R. ; O'Brien, Deborah A. ; Odet, Fanny ; Pakatci, Isa Kemal ; Pan, Wenqi ; de Villena, Fernando Pardo Manuel ; Perou, Charles M. ; Pomp, Daniel ; Quackenbush, Corey R. ; Robinson, Nashiya N. ; Sharpless, Norman E. ; Shaw, Ginger D. ; Spence, Jason S. ; Sullivan, Patrick F. ; Sun, Wei ; Tarantino, Lisa M. ; Valdar, William ; Wang, Jeremy ; Wang, Wei ; Welsh, Catherine E. ; Whitmore, Alan ; Wiltshire, Tim ; Wright, Fred A. ; Xie, Yuying ; Yun, Zaining ; Zhabotynsky, Vasyl ; Zhang, Zhaojun ; Zou, Fei ; Powell, Christine ; Steigerwalt, Jill ; Threadgill, David W. ; Chesler, Elissa J. ; Churchill, Gary A. ; Gatti, Daniel M. ; Korstanje, Ron ; Svenson, Karen L. ; Collins, Francis S. ; Crawford, Nigel ; Hunter, Kent ; Samir, N. ; Kelada, P. ; Peck, Bailey C.E. ; Reilly, Karlyne ; Tavarez, Urraca ; Bottomly, Daniel ; Hitzeman, Robert ; Mcweeney, Shannon K. ; Frelinger, Jeffrey ; Krovi, Harsha ; Phillippi, Jason ; Spritz, Richard A. ; Aicher, Lauri ; Katze, Michael ; Rosenzweig, Elizabeth ; Shusterman, Ariel ; Nashef, Aysar ; Weiss, Ervin I. ; Houri-Haddad, Yael ; Soller, Morris ; Williams, Robert ; Schughart, Klaus ; Yang, Hyuna ; French, John E. ; Benson, Andrew K. ; Kim, Jaehyoung ; Legge, Ryan ; Low, Soo Jen ; Ma, Fangrui ; Martinez, Ines ; Walter, Jens ; Broman, Karl W. ; Hallgrimsson, Benedikt ; Klein, Ophir ; Weinstock, George ; Warren, Wesley C. ; Yang, Yvana V. ; Schwartz, David. / The genome architecture of the collaborative cross mouse genetic reference population. In: Genetics. 2012 ; Vol. 190, No. 2. pp. 389-401.
@article{abf4363193134fc5ad77077e8078264a,
title = "The genome architecture of the collaborative cross mouse genetic reference population",
abstract = "The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multi parental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.",
author = "Iraqi, {Fuad A.} and Mustafa Mahajne and Yasser Salaymah and Hani Sandovski and Hanna Tayem and Karin Vered and Lois Balmer and Michael Hall and Glynn Manship and Grant Morahan and Ken Pettit and Jeremy Scholten and Kathryn Tweedie and Andrew Wallace and Lakshini Weerasekera and James Cleak and Caroline Durrant and Leo Goodstadt and Richard Mott and Binnaz Yalcin and Aylor, {David L.} and Baric, {Ralph S.} and Bell, {Timothy A.} and Bendt, {Katharine M.} and Jennifer Brennan and Brooks, {Jackie D.} and Buus, {Ryan J.} and Crowley, {James J.} and Calaway, {John D.} and Calaway, {Mark E.} and Agnieszka Cholka and Darr, {David B.} and Didion, {John P.} and Amy Dorman and Everett, {Eric T.} and Ferris, {Martin T.} and Mathes, {Wendy Foulds} and Fu, {Chen Ping} and Gooch, {Terry J.} and Goodson, {Summer G.} and Gralinski, {Lisa E.} and Hansen, {Stephanie D.} and Heise, {Mark T.} and Jane Hoel and Kunjie Hua and Kapita, {Mayanga C.} and Seunggeun Lee and Lenarcic, {Alan B.} and Liu, {Eric Yi} and Hedi Liu and Leonard McMillan and Magnuson, {Terry R.} and Manly, {Kenneth F.} and Miller, {Darla R.} and O'Brien, {Deborah A.} and Fanny Odet and Pakatci, {Isa Kemal} and Wenqi Pan and {de Villena}, {Fernando Pardo Manuel} and Perou, {Charles M.} and Daniel Pomp and Quackenbush, {Corey R.} and Robinson, {Nashiya N.} and Sharpless, {Norman E.} and Shaw, {Ginger D.} and Spence, {Jason S.} and Sullivan, {Patrick F.} and Wei Sun and Tarantino, {Lisa M.} and William Valdar and Jeremy Wang and Wei Wang and Welsh, {Catherine E.} and Alan Whitmore and Tim Wiltshire and Wright, {Fred A.} and Yuying Xie and Zaining Yun and Vasyl Zhabotynsky and Zhaojun Zhang and Fei Zou and Christine Powell and Jill Steigerwalt and Threadgill, {David W.} and Chesler, {Elissa J.} and Churchill, {Gary A.} and Gatti, {Daniel M.} and Ron Korstanje and Svenson, {Karen L.} and Collins, {Francis S.} and Nigel Crawford and Kent Hunter and N. Samir and P. Kelada and Peck, {Bailey C.E.} and Karlyne Reilly and Urraca Tavarez and Daniel Bottomly and Robert Hitzeman and Mcweeney, {Shannon K.} and Jeffrey Frelinger and Harsha Krovi and Jason Phillippi and Spritz, {Richard A.} and Lauri Aicher and Michael Katze and Elizabeth Rosenzweig and Ariel Shusterman and Aysar Nashef and Weiss, {Ervin I.} and Yael Houri-Haddad and Morris Soller and Robert Williams and Klaus Schughart and Hyuna Yang and French, {John E.} and Benson, {Andrew K.} and Jaehyoung Kim and Ryan Legge and Low, {Soo Jen} and Fangrui Ma and Ines Martinez and Jens Walter and Broman, {Karl W.} and Benedikt Hallgrimsson and Ophir Klein and George Weinstock and Warren, {Wesley C.} and Yang, {Yvana V.} and David Schwartz",
year = "2012",
month = "2",
day = "1",
doi = "10.1534/genetics.111.132639",
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TY - JOUR

T1 - The genome architecture of the collaborative cross mouse genetic reference population

AU - Iraqi, Fuad A.

AU - Mahajne, Mustafa

AU - Salaymah, Yasser

AU - Sandovski, Hani

AU - Tayem, Hanna

AU - Vered, Karin

AU - Balmer, Lois

AU - Hall, Michael

AU - Manship, Glynn

AU - Morahan, Grant

AU - Pettit, Ken

AU - Scholten, Jeremy

AU - Tweedie, Kathryn

AU - Wallace, Andrew

AU - Weerasekera, Lakshini

AU - Cleak, James

AU - Durrant, Caroline

AU - Goodstadt, Leo

AU - Mott, Richard

AU - Yalcin, Binnaz

AU - Aylor, David L.

AU - Baric, Ralph S.

AU - Bell, Timothy A.

AU - Bendt, Katharine M.

AU - Brennan, Jennifer

AU - Brooks, Jackie D.

AU - Buus, Ryan J.

AU - Crowley, James J.

AU - Calaway, John D.

AU - Calaway, Mark E.

AU - Cholka, Agnieszka

AU - Darr, David B.

AU - Didion, John P.

AU - Dorman, Amy

AU - Everett, Eric T.

AU - Ferris, Martin T.

AU - Mathes, Wendy Foulds

AU - Fu, Chen Ping

AU - Gooch, Terry J.

AU - Goodson, Summer G.

AU - Gralinski, Lisa E.

AU - Hansen, Stephanie D.

AU - Heise, Mark T.

AU - Hoel, Jane

AU - Hua, Kunjie

AU - Kapita, Mayanga C.

AU - Lee, Seunggeun

AU - Lenarcic, Alan B.

AU - Liu, Eric Yi

AU - Liu, Hedi

AU - McMillan, Leonard

AU - Magnuson, Terry R.

AU - Manly, Kenneth F.

AU - Miller, Darla R.

AU - O'Brien, Deborah A.

AU - Odet, Fanny

AU - Pakatci, Isa Kemal

AU - Pan, Wenqi

AU - de Villena, Fernando Pardo Manuel

AU - Perou, Charles M.

AU - Pomp, Daniel

AU - Quackenbush, Corey R.

AU - Robinson, Nashiya N.

AU - Sharpless, Norman E.

AU - Shaw, Ginger D.

AU - Spence, Jason S.

AU - Sullivan, Patrick F.

AU - Sun, Wei

AU - Tarantino, Lisa M.

AU - Valdar, William

AU - Wang, Jeremy

AU - Wang, Wei

AU - Welsh, Catherine E.

AU - Whitmore, Alan

AU - Wiltshire, Tim

AU - Wright, Fred A.

AU - Xie, Yuying

AU - Yun, Zaining

AU - Zhabotynsky, Vasyl

AU - Zhang, Zhaojun

AU - Zou, Fei

AU - Powell, Christine

AU - Steigerwalt, Jill

AU - Threadgill, David W.

AU - Chesler, Elissa J.

AU - Churchill, Gary A.

AU - Gatti, Daniel M.

AU - Korstanje, Ron

AU - Svenson, Karen L.

AU - Collins, Francis S.

AU - Crawford, Nigel

AU - Hunter, Kent

AU - Samir, N.

AU - Kelada, P.

AU - Peck, Bailey C.E.

AU - Reilly, Karlyne

AU - Tavarez, Urraca

AU - Bottomly, Daniel

AU - Hitzeman, Robert

AU - Mcweeney, Shannon K.

AU - Frelinger, Jeffrey

AU - Krovi, Harsha

AU - Phillippi, Jason

AU - Spritz, Richard A.

AU - Aicher, Lauri

AU - Katze, Michael

AU - Rosenzweig, Elizabeth

AU - Shusterman, Ariel

AU - Nashef, Aysar

AU - Weiss, Ervin I.

AU - Houri-Haddad, Yael

AU - Soller, Morris

AU - Williams, Robert

AU - Schughart, Klaus

AU - Yang, Hyuna

AU - French, John E.

AU - Benson, Andrew K.

AU - Kim, Jaehyoung

AU - Legge, Ryan

AU - Low, Soo Jen

AU - Ma, Fangrui

AU - Martinez, Ines

AU - Walter, Jens

AU - Broman, Karl W.

AU - Hallgrimsson, Benedikt

AU - Klein, Ophir

AU - Weinstock, George

AU - Warren, Wesley C.

AU - Yang, Yvana V.

AU - Schwartz, David

PY - 2012/2/1

Y1 - 2012/2/1

N2 - The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multi parental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.

AB - The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multi parental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.

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