Donald F. Conrad, Ph.D.
- Associate Professor, Oregon National Primate Research Center
- Chief, Division of Genetics, Oregon National Primate Research Center
Biography
Don Conrad, Ph.D. was recruited to OHSU in 2018 as chief of the newly established Division of Genetics at the Primate Center. He is a broadly trained human geneticist with over 15 years of experience in developing statistical and experimental methods for genome analysis. He obtained a Ph.D. in Human Genetics from the University of Chicago, studying with Dr. Jonathan Pritchard, and then did three years of post-doctoral training with Dr. Matthew Hurles at the Wellcome Trust Sanger Institute in Cambridge, UK. Before joining OHSU, Dr. Conrad was faculty at Washington University in St. Louis where he ran his own research group in the Department of Genetics, and was promoted to Associate Professor in 2017.
Dr. Conrad’s early career involved pioneering work in genome-scale analysis of DNA copy number variation (CNV), during which time he played a major role in mapping CNVs for numerous international genetics consortia and published what still stands as the highest resolution array-based map of human copy number variation. As a post-doc at the Sanger Institute he led the first analysis to compare the germline mutation rate among human families using whole genome sequencing.
Dr. Conrad is currently PI on two projects funded by the NIH. The first is to continue development of DeNovoGear, a software package for detecting de novo mutations from families, tissues and single cells, funded by NHGRI. The second is the GEMINI project, an international clinical consortium focusing on the genetics of male infertility, funded by NICHD. To date, GEMINI has exome sequenced about 1,000 cases of male infertility, and is now performing functional follow-up experiments on dozens of potentially novel genetic causes of infertility using animal models. As part of his involvement in GEMINI, Don is devising statistical methods for using large databases of genetic variation to assess the statistical significance of potential causal mutations in n=1 cases of rare disease.
The Conrad lab has a special interest in testis biology and has done work on a) developing methods for multiplex in vivo functional characterization of genes in testicular germ cells using shRNA and CRISPR b) purifying testicular cell populations c) mapping functional elements of germ cells genomes d) characterizing testis pathology using single cell RNA sequencing e) investigating the role of the immune system in regulation of spermatogenesis. Some of this work will be transitioned to non-human primates in order to capitalize on the environment at ONPRC.
Education and training
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Degrees
- A.B., 1999, Biochemistry and Molecular Biology - Dartmouth College
- M.Sc., 2000, Epidemiology, Stanford School of Medicine
- Ph.D., 2007, Human Genetics, The University of Chicago
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Fellowship
- Postdoctoral fellow, Wellcome Trust Sanger Institute, Cambridge, UK, 2007-2010
Memberships and associations:
- American Society of Human Genetics, 2005-present
- American Society of Andrology, 2010-present
- Editorial board of Andrology, 2012-present
- Editorial board of Biology of Reproduction, 2013-present
- Editorial board of Genome Research, 2014-present
- Society for the Study of Reproduction, 2018-present
Areas of interest
- Human genetics
- DNA mutation
- Infertility
- Genome biology of germ cells
- Single-cell genomics
Additional information
Honors and awards
- Fulbright Specialist Grant, 2017
- Finalist for Postdoctoral Trainee (Basic) award, ASHG, 2008
- Best Dissertation in Biological Sciences (honorable mention), The University of Chicago, 2008
Publications
Selected publications
- Chiang C, Scott AJ, Davis JR, Tsang EK, Li X, Kim Y, Hadzic T, Damani FN, Ganel L, GTEx Consortium, Montgomery SB, Battle A, Conrad DF, Hall IM. The impact of structural variation on human gene expression. Nat Genet. 2017 May; 49(5):692-699. PMC5406250.
- Ho NR, Usmani AR, Yin Y, Ma L, Conrad DF. Multiplex shRNA Screening of Germ Cell Development by in Vivo Transfection of Mouse Testis. G3 (Bethesda). 2017 Jan 5;7(1):247-255. PMC5217113.
- Wilfert AB, Chao KR, Kaushal M, Jain S, Zollner S, Adams DR, Conrad DF. Genome-wide significance testing of variation from single case exomes. Nat Genet. 2016 Dec;48(12):1455-1461. PMC5127779.
- MacArthur DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J, Abecasis GR, Adams DR, Altman RB, Antonarakis SE, Ashley EA, Barrett JC, Biesecker LG, Conrad DF, Cooper GM, Cox NJ, Daly MJ, Gerstein MB, Goldstein DB, Hirschhorn JN, Leal SM, Pennacchio LA, Stamatoyannopoulos JA, Sunyaev SR, Valle D, Voight BF, Winckler W, Gunter C. Guidelines for investigating causality of sequence variants in human disease. Nature. 2014. Apr 24;508(7497):469-476. PMC4180223.
- Ramu A, Noordam MJ, Schwartz RS, Wuster A, Hurles ME, Cartwright RS, Conrad DF. DeNovoGear: indel and point mutation discovery and phasing. Nat Methods 2013 Oct 10(1):985-987. PMC4003501.
- Lopes A, Aston K, Thompson E, Carvalho F, Gonçalves J, Huang N, Matthiesen R, Noordam MJ, Quintela I, Ramu A, Seabra C, Wilfert AB, Dai J, Downie JM, Fernandes S, Guo X, Sha J, Amorim A, Barros A, Carracedo A, Hu Z, Hurles ME, Moskovtsev S, Ober C, Paduch DA, Schiffman JD, Schlegel PN, Sousa M, Carrell DT, Conrad DF. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLoS Genetics 2013 Mar
- Conrad DF, Keebler JE, Depristo MA, Lindsay SJ, Zhang Y, Casals F, Idaghdour Y, Hartl CL, Torroja C, Garimella KV, Zilversmit M, Cartwright R, Rouleau GA, Daly M, Stone EA, Hurles ME, Awadalla P, on behalf of the 1000 genomes project. Variation in genome-wide mutation rates within and between human families. Nat Genet. 2011 Jun 12;43(7):712-714. PMC3322360.
- Conrad DF, Bird C, Blackburne B, Lindsay S, Mamanova L, Lee C, Turner DJ, Hurles ME. Mutation spectrum revealed by breakpoint sequencing of human germline CNVs. Nat Genet. 2010 May;42(5):385-391. PMC3428939.
- Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P, Fitzgerald T, Hu M, Ihm CH, Kristiansson K, Macarthur DG, Macdonald JR, Onyiah I, Pang AW, Robson S, Stirrups K, Valsesia A, Walter K, Wei J; Wellcome Trust Case Control Consortium, Tyler-Smith C, Carter NP, Lee C, Scherer SW, Hurles ME. Origins and functional impact of copy number variation in the human genome. Nature. 2010 Apr 1;464(7289):704-712. PMC3330748
- Conrad DF, Hurles ME. The population genetics of structural variation. Nat Genet. 2007 Jul;39(7 Suppl):S30-6. PMC2716079.
Publications
Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments
Proceedings of the National Academy of Sciences of the United States of AmericaPSAP-Genomic-Regions
Genetic EpidemiologyAXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans
Cell Death and DiseaseC19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line
Molecular CellDeleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects
Journal of cellular and molecular medicineGenetic mutation of Cep76 results in male infertility due to abnormal sperm tail composition
Life science allianceHeterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features
Human Genetics and Genomics AdvancesInherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility
Nature communicationsThe human infertility single-cell testis atlas (HISTA)
AndrologyToward clinical exomes in diagnostics and management of male infertility
American Journal of Human GeneticsUndiagnosed RASopathies in infertile men
Frontiers in EndocrinologyA naturally occurring variant of MBD4 causes maternal germline hypermutation in primates
Genome ResearchConsensus label propagation with graph convolutional networks for single-cell RNA sequencing cell type annotation
BioinformaticsDDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia
Communications BiologyGenome sequencing of Pakistani families with male infertility identifies deleterious genotypes in SPAG6, CCDC9, TKTL1, TUBA3C, and M1AP
AndrologyGenomic study of TEX15 variants
Frontiers in GeneticsIn vivo versus in silico assessment of potentially pathogenic missense variants in human reproductive genes
Proceedings of the National Academy of Sciences of the United States of AmericaRhesus macaque fetal and placental growth demographics
American Journal of PrimatologyTAD evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function
Nature communicationsThe origins and functional effects of postzygotic mutations throughout the human life span
ScienceActionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management
Human ReproductionA de novo paradigm for male infertility
Nature communicationsDDB1- and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential for male fertility in mice
Developmental BiologyDiverse monogenic subforms of human spermatogenic failure
Nature communicationsHuman INHBB Gene Variant (c.1079T>C:p.Met360Thr) Alters Testis Germ Cell Content, but Does Not Impact Fertility in Mice
EndocrinologyLarge-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic failure
American Journal of Human GeneticsSATINN
Bioinformatics