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RESEARCH ARTICLE
Contents Vol 47(6)

Bodyweight QTL on mouse chromosomes 4 and 11 by selective genotyping: regression v. maximum likelihood

Beben Benyamin A B D E , Ian C. A. Martin A , Carol C. Cheung C , Michael F. Buckley C , Peter C. Thomson A , Peter M. Visscher D and Chris Moran A
+ Author Affiliations
- Author Affiliations

A Centre for Advanced Technologies in Animal Genetics and Reproduction (Reprogen), University of Sydney, NSW 2006, Australia.

B Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JT, UK.

C Molecular and Cytogenetics Unit, South Eastern Area Laboratory Services, Department of Haematology, Prince of Wales Hospital, Sydney, NSW 2031, Australia.

D Genetic Epidemiology, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Qld 4029, Australia.

E Corresponding author. Email: bebenB@qimr.edu.au

Australian Journal of Experimental Agriculture 47(6) 677-682 https://doi.org/10.1071/EA06123
Submitted: 1 April 2006  Accepted: 18 October 2006   Published: 17 May 2007

Abstract

Two quantitative trait loci (QTL) for mouse bodyweight have previously been reported on mouse chromosomes (MMU) 4 and 11 from crosses of a highly fecund and large mouse strain, Inbred Quackenbush-Swiss 5 (QSi5) and C57Bl/6J. QSi5 has now been crossed with CBA/CaH to produce 1128 F2 mice to confirm the existence and effect of these QTL. In total, 226 mice from the upper and lower deciles for bodyweight were genotyped using 12 microsatellite markers covering MMU4 and MMU11. Regression and maximum likelihood based interval mapping by either including all mice (ungenotyped mice were treated as having missing genotypes) or including only selectively genotyped mice in the analyses were used to estimate the positions and effects of the QTL. The results confirmed the existence and effects of both QTL. Although all methods estimated the same QTL positions, the QTL effects were overestimated compared with the estimates using a suggested method (maximum likelihood by including all mice in the analysis). However, the overestimated QTL effects could be mathematically corrected. Since the confidence intervals of both QTL are still too large for positional cloning, an advanced intercross line is being bred for finely mapping these bodyweight QTL.


Acknowledgements

We would like to thank Dr Kyall Zenger for the initial screening of the microsatellite markers. Beben Benyamin would like to thank AusAID for providing the Australian Development Scholarship for pursuing a Master of Agriculture degree at the University of Sydney, Australia.


References


Brockmann GA, Bevova MR (2002) Using mouse models to dissect the genetics of obesity. Trends in Genetics 18, 367–376.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Brockmann GA, Haley CS, Renne U, Knott SA, Schwerin M (1998) Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth. Genetics 150, 369–381.
| PubMed |
open url image1

Brockmann GA, Kratzsch J, Haley CS, Renne U, Schwerin M, Karle S (2000) Single QTL effects, epistatis, and pleiotropy account for two-thirds of the phenotypic F2 variance of growth and obesity in DU61 × DBA/2 mice. Genome Research 10, 1941–1957.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cheung CC, Martin ICA, Zenger KR, Donald JA, Thomson PC, Moran C, Buckley MF (2004) Quantitative trait loci for steady-state platelet count in mice. Mammalian Genome 15, 784–797.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cheverud JM, Routman EJ, Duarte FAM, van Swinderen B, Cothran K, Perel C (1996) Quantitative trait loci for murine growth. Genetics 142, 1305–1319.
| PubMed |
open url image1

Corva PM, Medrano JF (2001) Quantitative trait loci (QTLs) mapping for growth traits in the mouse: a review. Genetics, Selection, Evolution. 33, 105–132.
| Crossref | GoogleScholarGoogle Scholar | open url image1

Darvasi A (1997) The effect of selective genotyping on QTL mapping accuracy. Mammalian Genome 8, 67–68.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Darvasi A, Soller M (1992) Selective genotyping for determination of linkage between a marker and a quantitative trait locus. Theoretical and Applied Genetics 85, 353–359.
| Crossref | GoogleScholarGoogle Scholar | open url image1

Darvasi A, Soller M (1995) Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141, 1199–1207.
| PubMed |
open url image1

Doerge RW (2002) Mapping and analysis of quantitative trait loci in experimental populations. Nature Reviews. Genetics 3, 43–52.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Falconer DS, Mackay TFC (1996) ‘Introduction to quantitative genetics.’ 4th edn. (Prentice Hall: Harlow, UK)

Haley CS, Knott SA (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.
| PubMed |
open url image1

Henshall JM, Goddard ME (1999) Multiple-trait mapping of quantitative trait loci after selective genotyping using logistic regression. Genetics 151, 885–894.
| PubMed |
open url image1

Hirayama I, Yi Z, Izumi S, Arai I, Suzuki W, Nagamuchi Y, Kuwano H, Takeuchi T, Izumi T (1999) Genetic analysis of obese diabetes in the TSOD mouse. Diabetes 48, 1183–1191.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Holt M, Nicholas FW, James JW, Moran C, Martin ICA (2004) Development of a highly-fecund inbred strain of mice. Mammalian Genome 15, 951–959.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Iraqi F, Clapcott SJ, Kumari P, Haley CS, Kemp SJ, Teale AJ (2000) Fine mapping of trypanosomiasis resistance loci in murine advanced intercross lines. Mammalian Genome 11, 645–648.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Johnson DL, Jansen RC, van Arendonk JAM (1999) Mapping quantitative trait loci in a selectively genotyped outbred population using a mixture model approach. Genetical Research 73, 75–83.
| Crossref | GoogleScholarGoogle Scholar | open url image1

Khatkar MS, Thomson PC, Tammen I, Raadsma HW (2004) Quantitative trait loci mapping in dairy cattle: review and meta-analysis. Genetics, Selection, Evolution. 36, 163–190.
| Crossref | GoogleScholarGoogle Scholar | open url image1

Kirkpatrick BW, Mengelt A, Schulman N, Martin ICA (1998) Identification of quantitative trait loci for prolificacy and growth in mice. Mammalian Genome 9, 97–102.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Knott SA (2005) Regression-based quantitative trait loci mapping: robust, efficient and effective. Philosophical Transactions of The Royal Society B 360, 1435–1442.
| Crossref | GoogleScholarGoogle Scholar | open url image1

Lander ES, Botstein D (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.
| PubMed |
open url image1

Lander ES, Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage result. Nature Genetics 11, 241–247.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

MGD (2002) Mouse Genome Database, Mouse Genome Informatics Web Site, The Jackson Laboratory, Bar Harbor, Maine. Available at http://www.informatics.jax.org [Verified 28 March 2007]

Moody DE, Pomp D, Nielsen MK, Van Vleck LD (1999) Identification of quantitative trait loci influencing traits related to energy balance in selection and inbred line of mice. Genetics 152, 699–711.
| PubMed |
open url image1

Morris KH, Ishikawa A, Keightley PD (1999) Quantitative trait loci for growth traits in C57BL/6J × DBA/2J mice. Mammalian Genome 10, 225–228.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Plum L, Kluge R, Giesen K, Altmüller J, Ortlepp JR, Joost HG (2000) Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice. Diabetes 49, 1590–1596.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Rocha JL, Eisen EJ, Van Vleck LD, Pomp D (2004) A large-sample QTL study in mice: I. Growth. Mammalian Genome 15, 83–99.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Sambrook J, Fritsch EF, Maniatis T (1989) ‘Molecular cloning: a laboratory manual.’ 2nd edn. (Cold Spring Harbour Laboratory Press: Cold Spring Harbor, NY)

Seaton G, Haley CS, Knott SA, Kearsey M, Visscher PM (2002) QTL Express: mapping quantitative trait loci in simple and complex pedigrees. Bioinformatics (Oxford, England) 18, 339–340.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Suto J, Matsuura S, Imamura K, Yamanaka H, Sekikawa K (1998) Genetics of obesity in KK mouse and effects of Ay allele on quantitative regulation. Mammalian Genome 9, 506–510.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Visscher PM, Thompson R, Haley CS (1996) Confidence intervals in QTL mapping by bootstrapping. Genetics 143, 1013–1020.
| PubMed |
open url image1

Wang S, Basten CJ, Zeng Z-B (2006) Windows QTL Cartographer 2.5. Department of Statistics, North Carolina State University, Raleigh, NC. Available at http://statgen.ncsu.edu/qtlcart/WQTLCart.htm [Verified 4 April 2007]

Xu S, Vogl C (2000) Maximum likelihood analysis of quantitative trait loci under selective genotyping. Heredity 84, 525–537.
| Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1