Chad Huff, PhD
Department of Epidemiology, Division of Cancer Prevention and Population Sciences
About Dr. Huff
My research is concentrated on understanding human evolution and the genetic basis of human disease through statistical, computational, and population genomics. My work spans a number of human genetics subdisciplines, including disease-gene identification, mutation rate estimation, detection of recent positive selection, and reconstruction of demographic history. I am currently focused on developing new methods to analyze genomic data and by applying these methods to discover novel insights about the genetic basis of human disease, with particular emphasis on identifying and characterizing genes that increase the risk of developing common cancers (colon, breast, head and neck, lung, pancreatic, prostate, and thyroid). Major Accomplishments
Strong publication record, with over 20 peer-reviewed papers, including three papers in Science, two in Nature Genetics, three in Genome Research, and one each in American Journal of Human Genetics, PLoS Genetics, and PNAS. Excellent progress in obtaining extramural funding in the first year as an independent investigator, with two established subcontracts, two submitted R01 proposals as a PI, and eight submitted R01 proposals as a co-investigator. Principal designer for the algorithm in the Variant Annotation, Analysis, and Search Tool (VAAST), which is a tool designed to identify disease-causing variation from next generation sequence data (Patent application number 61/381,239 ). Designed algorithm and software for the software package Estimation of Recent Shared Ancestry (ERSA), which greatly expands the range of familial relationships that can be detected from genomic data (Patent application number 61/433,921 ).
Research Interests
* Identifying intermediate-risk and high-risk cancer susceptibility loci from the analysis of rare genetic variation. * Developing methods and software to identify disease-causing genes from sequence data. * Developing new methods for pedigree analysis and cryptic relationship identification from genomic data. * Estimating human mutation rates. * Uncovering the genetic basis of recent positive selection in humans. * Reconstructing human demographic history.
Education & Training
Degree-Granting Education
| 2008 | University of Utah, Salt Lake City, UT, USA, PHD, Biological Anthropology |
| 2004 | University of Utah, Salt Lake City, UT, USA, MS, Biological Anthropology |
| 1996 | Missouri State University, Springfield, MO, USA, BA, Computer Information Systems |
Selected Publications
Peer-Reviewed Articles
- Hu H, Huff CD. Detecting Statistical Interaction Between Somatic Mutational Events and Germline Variation from Next-Generation Sequence Data. Pac Symp Biocomput:51-62, 2014. PMID: 24297533.
- Hu H, Huff CD, Moore B, Flygare S, Reese MG, Yandell M. VAAST 2.0: Improved Variant Classification and Disease-gene Identification Using a Conservation-Controlled Amino Acid Substitution Matrix. Genet Epidemiol 37(6):622-34, 2013. e-Pub 2013. PMID: 23836555.
- Xing J, Wuren T, Simonson TS, Watkins WS, Witherspoon DJ, Wu W, Qin G, Huff CD, Jorde LB, Ge RL. Genomic analysis of natural selection and phenotypic variation in high-altitude mongolians. PLoS Genet 9(7):e1003634, 2013. e-Pub 2013. PMID: 23874230.
- Tomasic NL, Piterkova L, Huff CH, Bilic E, Yoon D, Miasnikova GY, Sergueeva AI, Niu X, Nekhai S, Gordeuk V, Prchal JT. Polycythemia due to Croatian homozygous VHL (571C>G:H191D) mutation has a different phenotype than Chuvash polycythemia (VHL 598C>T:R200W). Haematologica 98(4):560-7, 2013. e-Pub 2013. PMID: 23403324.
- Shapiro MD, Kronenberg Z, Li C, Domyan ET, Pan H, Campbell M, Tan H, Huff CD, Hu H, Vickrey AI, Nielsen SC, Stringham SA, Willerslev E, Gilbert MT, Yandell M, Zhang G, Wang J. Genomic Diversity and Evolution of the Head Crest in the Rock Pigeon. Science 339(6123):1063-7, 2013. e-Pub 2013. PMID: 23371554.
- Coon H, Darlington T, Pimentel R, Smith KR, Huff CD, Hu H, Jerominski L, Hansen J, Klein M, Callor WB, Byrd J, Bakian A, Crowell SE, McMahon WM, Rajamanickam V, Camp NJ, McGlade E, Yurgelun-Todd D, Grey T, Gray D. Genetic Risk Factors in two Utah Pedigrees at High Risk for Suicide. Transl Psychiatry 3:e325, 2013. e-Pub 2013. PMID: 24252905.
- Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E, European Alternating Hemiplegia of Childhood (AHC) Genetics Consortium, Nicole S, Gurrieri F, Neri G, de Vries B, Koelewijn S, Kamphorst J, Geilenkirchen M, Pelzer N, Laan L, Haan J, Ferrari M, van den Maagdenberg A, Biobanca e Registro Clinico per l'Emiplegia Alternante (I.B.AHC) Consortium, Zucca C, Bassi MT, Franchini F, Vavassori R, Giannotta M, Gobbi G, Granata T, Nardocci N, De Grandis E, Veneselli E, Stagnaro M, Gurrieri F, Neri G, Vigevano F, European Network for Research on Alternating Hemiplegia (ENRAH) for Small and Medium-sized Enterpriese (SMEs) Consortium, Panagiotakaki E, Oechsler C, Arzimanoglou A, Nicole S, Giannotta M, Gobbi G, Ninan M, Neville B, Ebinger F, Fons C, Campistol J, Kemlink D, Nevsimalova S, Laan L, Peeters-Scholte C, van den Maagdenberg A, Casaer P, Casari G, Sange G, Spiel G, Martinelli Boneschi F, Zucca C, Bassi MT, Schyns T, Crawley F, Poncelin D, Vavassori R, Fiori S, Abiusi E, Di Pietro L, Sweney MT, Newcomb TM, Viollet L, Huff CD, Jorde LB, Reyna SP, Murphy KJ, Shianna KV, Gumbs CE, Little L, Silver K, Ptácek LJ, Haan J, Ferrari MD, Bye AM, Herkes GK, Whitelaw CM, Webb D, Lynch BJ, Uldall P, King MD, Scheffer IE, Neri G, Arzimanoglou A, van den Maagdenberg AM, Sisodiya SM, Mikati MA, Goldstein DB. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet 44(9):1030-4, 2012. e-Pub 2012. PMID: 22842232.
- Ge RL, Simonson TS, Cooksey RC, Tanna U, Qin G, Huff CD, Witherspoon DJ, Xing J, Zhengzhong B, Prchal JT, Jorde LB, McClain DA. Metabolic insight into mechanisms of high-altitude adaptation in Tibetans. Mol Genet Metab 106(2):244-7, 2012. e-Pub 2012. PMID: 22503288.
- Huff CD, Witherspoon DJ, Zhang Y, Gatenbee C, Denson LA, Kugathasan S, Hakonarson H, Whiting A, Davis CT, Wu W, Xing J, Watkins WS, Bamshad MJ, Bradfield JP, Bulayeva K, Simonson TS, Jorde LB, Guthery SL. Crohn's disease and genetic hitchhiking at IBD5. Mol Biol Evol 29(1):101-11, 2012. e-Pub 2011. PMID: 21816865.
- Watkins W S, Xing J, Huff CD, Witherspoon D, Zhang Y, Perego U, Woodward S, Jorde LB. Genetic analysis of ancestry, admixture and selection in Bolivian and Totonac populations of the New World. BMC Genetics 13(1):39, 2012.
- Yandell M*, Huff C*, Hu H*, Singleton M, Moore B, Xing J, Jorde LB, Reese MG. A probabilistic disease-gene finder for personal genomes. Genome Res 21(9):1529-42, 2011. e-Pub 2011. PMID: 21700766.
- Rope AF, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ, Johnson WE, Moore B, Huff CD, Bird LM, Carey JC, Opitz JM, Stevens CA, Jiang T, Schank C, Fain HD, Robison R, Dalley B, Chin S, South ST, Pysher TJ, Jorde LB, Hakonarson H, Lillehaug JR, Biesecker LG, Yandell M, Arnesen T, Lyon GJ. Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency. Am J Hum Genet 89(1):28-43, 2011. e-Pub 2011. PMID: 21700266.
- Huff CD*, Witherspoon DJ*, Simonson TS, Xing J, Watkins WS, Zhang Y, Tuohy TM, Neklason DW, Burt RW, Guthery SL, Woodward SR, Jorde LB, *Co-First Author. Maximum-likelihood estimation of recent shared ancestry (ERSA). Genome Res 21(5):768-74, 2011. e-Pub 2011. PMID: 21324875.
- Simonson TS, Xing J, Barrett R, Jerah E, Loa P, Zhang Y, Watkins WS, Witherspoon DJ, Huff CD, Woodward S, Mowry B, Jorde LB. Ancestry of the Iban is predominantly Southeast Asian: genetic evidence from autosomal, mitochondrial, and Y chromosomes. PLoS One 6(1):e16338, 2011. e-Pub 2011. PMID: 21305013.
- Stewart C, Kural D, Strömberg MP, Walker JA, Konkel MK, Stütz AM, Urban AE, Grubert F, Lam HYK, Lee WP, Busby M, Indap AR, Garrison E, Huff CD, Xing J, Snyder MP, Jorde LB, Batzer MA, Korbel JO, Marth GT, 1000 Genomes Project (2011). A comprehensive map of mobile element insertion polymorphisms in humans. PLoS Genetics 7(8):e1002236, 2011.
- Xing J, Watkins WS, Shlien A, Walker E, Huff CD, Witherspoon DJ, Zhang Y, Simonson TS, Weiss RB, Schiffman JD, Malkin D, Woodward SR, Jorde LB. Toward a more uniform sampling of human genetic diversity: a survey of worldwide populations by high-density genotyping. Genomics 96(4):199-210, 2010. e-Pub 2010. PMID: 20643205.
- Simonson TS, Yang Y, Huff CD, Yun H, Qin G, Witherspoon DJ, Bai Z, Lorenzo FR, Xing J, Jorde LB, Prchal JT, Ge R. Genetic evidence for high-altitude adaptation in Tibet. Science 329(5987):72-5, 2010. e-Pub 2010. PMID: 20466884.
- Roach JC*, Glusman G*, Smit AF*, Huff CD*, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, Shendure J, Drmanac R, Jorde LB, Hood L, Galas DJ, *Co-First Author. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328(5978):636-9, 2010. e-Pub 2010. PMID: 20220176.
- Simonson TS, Zhang Y, Huff CD, Xing J, Watkins WS, Witherspoon DJ, Woodward SR, Jorde LB. Limited distribution of a cardiomyopathy-associated variant in India. Ann Hum Genet 74(2):184-8, 2010. e-Pub 2010. PMID: 20201939.
- Huff CD, Xing J, Rogers AR, Witherspoon D, Jorde LB. Mobile elements reveal small population size in the ancient ancestors of Homo sapiens. Proc Natl Acad Sci U S A 107(5):2147-52, 2010. e-Pub 2010. PMID: 20133859.
- Huff CD, Harpending HC, Rogers AR. Detecting positive selection from genome scans of linkage disequilibrium. BMC Genomics 11:8, 2010. e-Pub 2010. PMID: 20051139.
- Xing J, Watkins WS, Hu Y, Huff CD, Sabo A, Muzny DM, Bamshad MJ, Gibbs RA, Jorde LB, Yu F. Genetic diversity in India and the inference of Eurasian population expansion. Genome Biol 11(11):R113, 2010. e-Pub 2010. PMID: 21106085.
- Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42(1):30-5, 2010. e-Pub 2009. PMID: 19915526.
- Xing J, Zhang Y, Han K, Salem AH, Sen SK, Huff CD, Zhou Q, Kirkness EF, Levy S, Batzer MA, Jorde LB. Mobile elements create structural variation: analysis of a complete human genome. Genome Res 19(9):1516-26, 2009. e-Pub 2009. PMID: 19439515.
- Smith SE, Hayes MG, Cabana GS, Huff CD, Coltrain JB, O'Rourke DH. Inferring population continuity versus replacement with a DNA: A cautionary tale from the Aleutian Islands. Hum Biol 81(4):407-726, 2009.
- Rogers AR, Huff CD. Linkage disequilibrium between loci with unknown phase. Genetics 182:834-839, 2009.
- Rogers AR, Wooding S, Huff CD, Batzer MA, Jorde LB. Ancestral alleles and population origins: inferences depend on mutation rate. Mol Biol Evol 24(4):990-7, 2007. e-Pub 2007. PMID: 17267423.
Grant & Contract Support
| Title: | Massively Parallel Sequencing for Familiar Colon Cancer Genes |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator-MDACC |
| Title: | Transdisciplinary Research in Cancer of the Lung (TRICL) ; Area 3: Epidemiologic Architecture of Lung Cancer and Smoking |
| Funding Source: | NIH/NCI |
| Role: | Co-Investigator |
| Title: | Integrating Physiology and Genomics to Reveal Functional Adaptation in High-Altitude Tibetans |
| Funding Source: | NIH/NHLBI |
| Role: | Principal Investigator-MDACC |
| Title: | VAAST+: tool for variant prioritization, risk assessment, and disease-gene finding |
| Funding Source: | NIH/NIGMS |
| Role: | Principal Investigator-MDACC |
| Title: | Genetic Analysis of Anticipation in Lynch Syndrome |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Co-Investigator |
| Title: | Next-Generation Sequencing to Identify and Characterize Breast Cancer Risk Genes in Hispanic American Women |
| Funding Source: | Andrew Sabin Family Fellows Award |
| Role: | Principal Investigator |