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A computational method for genotype calling in family-based sequencing data

Chang, LC and Li, B and Fang, Z and Vrieze, S and McGue, M and Iacono, WG and Tseng, GC and Chen, W (2016) A computational method for genotype calling in family-based sequencing data. BMC Bioinformatics, 17 (1).

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Background: As sequencing technologies can help researchers detect common and rare variants across the human genome in many individuals, it is known that jointly calling genotypes across multiple individuals based on linkage disequilibrium (LD) can facilitate the analysis of low to modest coverage sequence data. However, genotype-calling methods for family-based sequence data, particularly for complex families beyond parent-offspring trios, are still lacking. Results: In this study, first, we proposed an algorithm that considers both linkage disequilibrium (LD) patterns and familial transmission in nuclear and multi-generational families while retaining the computational efficiency. Second, we extended our method to incorporate external reference panels to analyze family-based sequence data with a small sample size. In simulation studies, we show that modeling multiple offspring can dramatically increase genotype calling accuracy and reduce phasing and Mendelian errors, especially at low to modest coverage. In addition, we show that using external panels can greatly facilitate genotype calling of sequencing data with a small number of individuals. We applied our method to a whole genome sequencing study of 1339 individuals at ~10X coverage from the Minnesota Center for Twin and Family Research. Conclusions: The aggregated results show that our methods significantly outperform existing ones that ignore family constraints or LD information. We anticipate that our method will be useful for many ongoing family-based sequencing projects. We have implemented our methods efficiently in a C++ program FamLDCaller, which is available from


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Chang, LC
Li, B
Fang, Zzhf9@pitt.eduZHF9
Vrieze, S
McGue, M
Iacono, WG
Tseng, GCctseng@pitt.eduCTSENG
Chen, Wwei.chen@pitt.eduWEC47
Date: 16 January 2016
Date Type: Publication
Journal or Publication Title: BMC Bioinformatics
Volume: 17
Number: 1
DOI or Unique Handle: 10.1186/s12859-016-0880-5
Schools and Programs: School of Public Health > Biostatistics
School of Medicine > Immunology
Refereed: Yes
Date Deposited: 25 Jul 2016 17:46
Last Modified: 10 Jun 2023 11:55


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