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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1993 Jul;53(1):252–263.

Faster sequential genetic linkage computations.

R W Cottingham Jr 1, R M Idury 1, A A Schäffer 1
PMCID: PMC1682239  PMID: 8317490

Abstract

Linkage analysis using maximum-likelihood estimation is a powerful tool for locating genes. As available data sets have grown, the computation required for analysis has grown exponentially and become a significant impediment. Others have previously shown that parallel computation is applicable to linkage analysis and can yield order-of-magnitude improvements in speed. In this paper, we demonstrate that algorithmic modifications can also yield order-of-magnitude improvements, and sometimes much more. Using the software package LINKAGE, we describe a variety of algorithmic improvements that we have implemented, demonstrating both how these techniques are applied and their power. Experiments show that these improvements speed up the programs by an order of magnitude, on problems of moderate and large size. All improvements were made only in the combinatorial part of the code, without restoring to parallel computers. These improvements synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.

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Selected References

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  1. Blanton S. H., Heckenlively J. R., Cottingham A. W., Friedman J., Sadler L. A., Wagner M., Friedman L. H., Daiger S. P. Linkage mapping of autosomal dominant retinitis pigmentosa (RP1) to the pericentric region of human chromosome 8. Genomics. 1991 Dec;11(4):857–869. doi: 10.1016/0888-7543(91)90008-3. [DOI] [PubMed] [Google Scholar]
  2. Dausset J., Cann H., Cohen D., Lathrop M., Lalouel J. M., White R. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics. 1990 Mar;6(3):575–577. doi: 10.1016/0888-7543(90)90491-c. [DOI] [PubMed] [Google Scholar]
  3. Elston R. C., Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. doi: 10.1159/000152448. [DOI] [PubMed] [Google Scholar]
  4. Goradia T. M., Lange K., Miller P. L., Nadkarni P. M. Fast computation of genetic likelihoods on human pedigree data. Hum Hered. 1992;42(1):42–62. doi: 10.1159/000154045. [DOI] [PubMed] [Google Scholar]
  5. Lange K., Elston R. C. Extensions to pedigree analysis I. Likehood calculations for simple and complex pedigrees. Hum Hered. 1975;25(2):95–105. doi: 10.1159/000152714. [DOI] [PubMed] [Google Scholar]
  6. Lange K., Goradia T. M. An algorithm for automatic genotype elimination. Am J Hum Genet. 1987 Mar;40(3):250–256. [PMC free article] [PubMed] [Google Scholar]
  7. Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
  8. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lathrop G. M., Lalouel J. M., White R. L. Construction of human linkage maps: likelihood calculations for multilocus linkage analysis. Genet Epidemiol. 1986;3(1):39–52. doi: 10.1002/gepi.1370030105. [DOI] [PubMed] [Google Scholar]
  10. Law A., Richard C. W., 3rd, Cottingham R. W., Jr, Lathrop G. M., Cox D. R., Myers R. M. Genetic linkage analysis of bipolar affective disorder in an Old Order Amish pedigree. Hum Genet. 1992 Mar;88(5):562–568. doi: 10.1007/BF00219345. [DOI] [PubMed] [Google Scholar]
  11. Miller P. L., Nadkarni P., Gelernter J. E., Carriero N., Pakstis A. J., Kidd K. K. Parallelizing genetic linkage analysis: a case study for applying parallel computation in molecular biology. Comput Biomed Res. 1991 Jun;24(3):234–248. doi: 10.1016/0010-4809(91)90046-y. [DOI] [PubMed] [Google Scholar]
  12. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]

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