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Computational methods for calculating meiotic recombination from nuclear pedigrees

Mukhopadhyay, Nandita (2016) Computational methods for calculating meiotic recombination from nuclear pedigrees. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Meiotic recombination is increasingly an important area for research in genetics. Recombination is critical for the proper segregation of chromosomes, and errors in recombination may result in chromosomal abnormalities and non-disjunction. Both the total number and the pattern of recombination events are known to vary genome-wide and from person to person. Using genome-wide genotype data to detect locations of recombination in individuals is the first necessary tool to study recombination. Earlier methods, e.g. CRI-MAP, used linkage-style modeling on three-generation families and sparse microsatellite markers to detect recombination events. More recently, methods using “streaks” of SNPs showing IBD status on dense GWAS SNP data have been used to score recombination locations in sibships. Here, I have developed a new SNP streak method to score recombination locations in pedigree types not previously handled, such as half-sibling pedigrees, and pedigrees with one or more ungenotyped individuals. We implemented our new method as a Python software package, MBFam. This package analyzes family-based genome-wide association datasets, accepting input data as PLINK binary files, a widely used input format for genetic data. The computation steps involve extraction of recombination probands, detection of recombination events, computation of recombination breakpoint locations and the offspring inheriting each recombination event, while accounting for Mendelian inheritance inconsistency errors and proximate double recombinations. MBFam has been extensively tested on the Mac OSX and Linux platforms. For demonstration purposes, this new method was applied to two family-based GWAS datasets. Recombination intervals scored were used to create sex-specific average recombination counts (ARC) using all new pedigree structures and only the full-sibships. GWASs were conducted for male and female probands for both sets of ARCs. In one of the datasets, the added pedigree structures increased the female proband sample. This new method has the potential to significantly improve sample sizes for recombination studies, eventually leading to a better understanding of the biology of recombination and fertility, and benefitting the design of medical and public health interventions for improving maternal and child health.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Mukhopadhyay, Nanditanandita@pitt.eduNANDITA
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberMarazita, Mary L.marazita@pitt.eduMARAZITA
Committee MemberWeeks, Daniel E.weeks@pitt.eduWEEKS0000-0001-9410-7228
Committee MemberKammerer, Candace Mcmk3@pitt.eduCMK3
Date: 29 June 2016
Date Type: Publication
Defense Date: 29 March 2016
Approval Date: 29 June 2016
Submission Date: 11 May 2016
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 93
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Recombination Pedigree Genomewide recombination rate Recombination phenotype Genomewide association study SNP association panel
Date Deposited: 29 Jun 2016 17:38
Last Modified: 30 Jun 2022 15:23


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