Evidence of a Large-scale Functional Organization of Mammalian Chromosomes

Overview

Journal PLoS Genet

Specialty Genetics

Date 2005 Sep 16

PMID 16163395

Citations 63

Authors

Petko M Petkov

Joel H Graber

Gary A Churchill

Keith DiPetrillo

Benjamin L King

Kenneth Paigen

Affiliations

Soon will be listed here.

Abstract

Evidence from inbred strains of mice indicates that a quarter or more of the mammalian genome consists of chromosome regions containing clusters of functionally related genes. The intense selection pressures during inbreeding favor the coinheritance of optimal sets of alleles among these genetically linked, functionally related genes, resulting in extensive domains of linkage disequilibrium (LD) among a set of 60 genetically diverse inbred strains. Recombination that disrupts the preferred combinations of alleles reduces the ability of offspring to survive further inbreeding. LD is also seen between markers on separate chromosomes, forming networks with scale-free architecture. Combining LD data with pathway and genome annotation databases, we have been able to identify the biological functions underlying several domains and networks. Given the strong conservation of gene order among mammals, the domains and networks we find in mice probably characterize all mammals, including humans.

Citing Articles

A multiomic network approach uncovers disease modifying mechanisms of inborn errors of metabolism.

Bender A, Ranea-Robles P, Williams E, Williams E, Mirzaian M, Heimel J bioRxiv. 2025; .

PMID: 40027804 PMC: 11870498. DOI: 10.1101/2025.02.19.639093.

An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development.

Lin C, Ellegood J, Tamada K, Miura I, Konda M, Takeshita K Mol Psychiatry. 2023; 28(5):1932-1945.

PMID: 36882500 PMC: 10575786. DOI: 10.1038/s41380-023-01999-z.

A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization.

Raza A, Diehl S, Krementsov D, Case L, Li D, Kost J Commun Biol. 2023; 6(1):244.

PMID: 36879097 PMC: 9988836. DOI: 10.1038/s42003-023-04603-w.

Genetic Background Matters: Population-Based Studies in Model Organisms for Translational Research.

Olguin V, Duran A, Heras M, Rubilar J, Cubillos F, Olguin P Int J Mol Sci. 2022; 23(14).

PMID: 35886916 PMC: 9316598. DOI: 10.3390/ijms23147570.

Modeling allelic diversity of multiparent mapping populations affects detection of quantitative trait loci.

Odell S, Hudson A, Praud S, Dubreuil P, Tixier M, Ross-Ibarra J G3 (Bethesda). 2022; 12(3).

PMID: 35100382 PMC: 8895984. DOI: 10.1093/g3journal/jkac011.

References

Bourque G, Pevzner P, Tesler G . Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes. Genome Res. 2004; 14(4):507-16. PMC: 383294. DOI: 10.1101/gr.1975204. View

Oster S, Ho C, Soucie E, Penn L . The myc oncogene: MarvelouslY Complex. Adv Cancer Res. 2002; 84:81-154. DOI: 10.1016/s0065-230x(02)84004-0. View

Sarkar S, Leaman D, Gupta S, Sil P, Young D, Morehead A . Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice. J Biol Chem. 2004; 279(19):20422-34. DOI: 10.1074/jbc.M308488200. View

Hurst L, Pal C, Lercher M . The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet. 2004; 5(4):299-310. DOI: 10.1038/nrg1319. View

Yalcin B, Fullerton J, Miller S, Keays D, Brady S, Bhomra A . Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice. Proc Natl Acad Sci U S A. 2004; 101(26):9734-9. PMC: 470780. DOI: 10.1073/pnas.0401189101. View

Teichmann S, Veitia R . Genes encoding subunits of stable complexes are clustered on the yeast chromosomes: an interpretation from a dosage balance perspective. Genetics. 2004; 167(4):2121-5. PMC: 1471008. DOI: 10.1534/genetics.103.024505. View

Petkov P, Ding Y, Cassell M, Zhang W, Wagner G, Sargent E . An efficient SNP system for mouse genome scanning and elucidating strain relationships. Genome Res. 2004; 14(9):1806-11. PMC: 515327. DOI: 10.1101/gr.2825804. View

Nei M . Modification of linkage intensity by natural selection. Genetics. 1967; 57(3):625-41. PMC: 1211753. DOI: 10.1093/genetics/57.3.625. View

Smith T, Waterman M . Identification of common molecular subsequences. J Mol Biol. 1981; 147(1):195-7. DOI: 10.1016/0022-2836(81)90087-5. View

10.

Guenet J . Do non-linked genes really reassort at random?. Ann Inst Pasteur Immunol (1985). 1985; 136C(1):85-90. View

11.

Hedrick P . Gametic disequilibrium measures: proceed with caution. Genetics. 1987; 117(2):331-41. PMC: 1203208. DOI: 10.1093/genetics/117.2.331. View

12.

Saitou N, Nei M . The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987; 4(4):406-25. DOI: 10.1093/oxfordjournals.molbev.a040454. View

13.

Christner R, Mortensen R . Specificity of the binding interaction between human serum amyloid P-component and immobilized human C-reactive protein. J Biol Chem. 1994; 269(13):9760-6. View

14.

Lewontin R . The detection of linkage disequilibrium in molecular sequence data. Genetics. 1995; 140(1):377-88. PMC: 1206563. DOI: 10.1093/genetics/140.1.377. View

15.

Devlin B, Risch N . A comparison of linkage disequilibrium measures for fine-scale mapping. Genomics. 1995; 29(2):311-22. DOI: 10.1006/geno.1995.9003. View

16.

Zapata C, Alvarez G . On Fisher's exact test for detecting gametic disequilibrium between DNA polymorphisms. Ann Hum Genet. 1997; 61(Pt 1):71-7. DOI: 10.1046/j.1469-1809.1997.6110069.x. View

17.

Su A, Cooke M, Ching K, Hakak Y, Walker J, Wiltshire T . Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A. 2002; 99(7):4465-70. PMC: 123671. DOI: 10.1073/pnas.012025199. View

18.

Kaneto H, Sharma A, Suzuma K, Laybutt D, Xu G, Bonner-Weir S . Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activation. J Biol Chem. 2002; 277(15):12998-3006. DOI: 10.1074/jbc.M111148200. View

19.

Gabriel S, Schaffner S, Nguyen H, Moore J, Roy J, Blumenstiel B . The structure of haplotype blocks in the human genome. Science. 2002; 296(5576):2225-9. DOI: 10.1126/science.1069424. View

20.

Dawson E, Abecasis G, Bumpstead S, Chen Y, Hunt S, Beare D . A first-generation linkage disequilibrium map of human chromosome 22. Nature. 2002; 418(6897):544-8. DOI: 10.1038/nature00864. View