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USC College > Faculty > Departments > Department of Biological Sciences > Norman Arnheim
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Norman Arnheim

Distinguished Professor, Ester Dornsife Chair in Biological Sciences, and Professor of Biological Sciences and Biochemistry

Contact Information
Office: RRI 319C
Phone: (213)740-7675
E-mail: arnheim@usc.edu

 

Education
B.A. Biology, University of Rochester, 1/1960
M.S. Biology, University of Rochester, 1/1962
Ph.D. Genetics, University of California, Berkeley, 1/1965
 

Description of Research

Summary Statement of Research Interests
A major interest of our lab is recombination and mutation in the human germline and the relation between these processes and human genetic disease. We are using single molecule PCR analysis to study the patterns of mutational change that occur at loci containing repeated DNA sequences. Our studies on human mutation focus on loci that exhibit the paternal age effect. An example is the locus that codes for the FGFR3 protein. Mutations in this protein cause achondroplasia, the most common form of dwarfism. It has been known for a long time that the older a man gets, the more likely it is that he will have children with this mutation. The basic premise of the paternal age effect is that as men age, they produce more sperm carrying a de novo mutation. Attempts to use sperm DNA to test this assumption were made for the first time only within the last few years. We are interested in two major features of the paternal age effect; 1) the reason for the fact that mutations that exhibit the paternal age effect occur only in males and 2) why the mutation rate is 100-1000 times greater for these mutations than the average rate. We are also interested in understanding the factors that determine why some human chromosome regions undergo genetic recombination at a much higher frequency than others. This project is important to the attempts to map disease gene loci using so called "association mapping" with single nucleotide polymorphisms (SNPs). In order to gain information on the distribution of recombination events at very high resolution we use a method of allele-specific PCR that can detect rare recombinants in a pooled sample of sperm DNA. This data is being used to study how well recombination can explain linkage disequilibrium across the human genome and how well in silico methods can predict the position of recombination hot spots (regions that have a much higher frequency of crossing over than the surrounding sequences). Our data can also be used to help define the birth and death process of recombination hot spots during evolution.
 

Research Specialties
Aging and Development Biology, Biochemistry, Molecular Biology
 

Affiliations with Research Centers, Labs, and Other Institutions
Center for Computational & Experimental Genomics,http://www-hto.usc.edu/
Department of Biological Sciences,http://www.usc.edu/dept/LAS/biosci/
 

Publications

Journal Article
., .. (2007). Clark V, Ptak SE, Tiemann-Boege I, Gian Y, Coop G, Stone AC, Przeworski M, Arnheim N, Di Rienzo A. (2007) Combining sperm typing and LD analyses reveals differences in selective pressures or recombination rates across human populations. Genetics. 175(2):795-804.
., .. (2007). Shelbourne, PF, Keller-McGandy, C, Bi, WL, Yoon, SR, Dubeau, L, Veitch, NJ, Vonsattel, JP, Wexler, NX and the Venezuela Huntington Disease Project, Arnheim, N, Augood, SJ. (2007) Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Human Molecular Genetics. 16(10):1133-1142.
QIN, J., Calabrese, P., Tiemann-Boege, I. I., Shinde, D. N., Yoon, S. R. (2007). The molecular anatomy of spontaneous germline mutations in human testes. PLOS Biology. Sep;5(9):e224.
., .. (2006). Wyrobek AJ, Eskenazi B, Young S, Arnheim N, Tiemann-Boege I, Jabs EW, Glaser RL, Pearson FS, Evenson D. (2006) Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci U S A. 103(25):9601-6.
., .. (2006). Wesoly J, Agarwal S, Sigurdsson S, Bussen W, Van Komen S, Qin J, van Steeg, H, van Benthem J, Wassenaar E, Baarends WM, Ghazvini M, Tafel AA, Heath H, Galjart N, Essers J, Grootegoed JA, Arnheim N, Bezzubova O, Buerstedde JM, Sung P, Kanaar R. (2006) Differential contributions of Mammalian rad54 paralogs to recombination, DNA damage repair, and meiosis. Mol Cell Biol. 26(3):976-89.
., .. (2006). Tiemann-Boege, I. Calabrese, P., Cochran, D.C., Sokol, R.Z., Arnheim, N. (2006) High Resolution Recombination Patterns in a Region of Human Chromosome 21 Measured by Sperm Typing. PLoS Genetics 2(5): e70.
., .. (2005). Subramanian, J., Vijayakumar, S., Tomkinson, A. and Arnheim, N. (2005) Genetic Instability Induced by Overexpression of DNA ligase I in Budding Yeast. Genetics. 171(2):427-41. Genetics. Vol. 171(2), pp. 427-41.
., .. (2005). Tiemann-Boege, I. Calabrese, P., Cochran, D.C., Sokol, R.Z., Arnheim, N. (2006) High Resolution Recombination Patterns in a Region of Human Chromosome 21 Measured by Sperm Typing. PLoS Genetics 2(5): e70.
., .. (2005). Chen PC, Dudley S, Hagen W, Dizon D, Paxton L, Reichow D, Yoon SR, Yang K, Arnheim N, Liskay RM, Lipkin SM.. (2005) Contributions by MutL Homologs Mlh3 and Pms2 to DNA Mismatch Repair and Tumor Suppression in the Mouse. Cancer Research, 65(19):8662-70.
., .. (2004). Brohede, J., Arnheim, N. and Ellegren, H. (2004) Single molecule analysis of the hypermutable tetranucleotide repeat locus D21S1245 through sperm genotyping: a heterogeneous pattern of mutation but no clear male age effect. Molecular Biology and Evolution: 21:58-64.
., .. (2003). Shinde, D., Lai, Y., Sun, F. and Arnheim, N. (2003) Taq DNA polymerase slippage mutation rates measured by PCR and quasi-likelihood analysis: (CA/GT)(n) and (A/T)(n) microsatellites. Nucleic Acids Res. 31(3):974-80.
., .. (2003). Nenguke, T., Aladjem, M.I., Gusella, J.F., Wexler, N.S. and the Venezuela HD Project and Arnheim, N. (2003) Candidate DNA replication initiation regions at human trinucleotide repeat disease loci. Human Molecular Genetics, 12:1021-1028.
., .. (2003). Arnheim, N., Calabrese, P. and Nordborg, N. (2003) Hot and cold spots of recombination in the Human genome: the reason we should find them and how this can be achieved. Am. J. Hum. Genet 73: 5-16.
., .. (2003). Yoon, S-R., Dubeau, L., de Young, M., Wexler, N.S. and Arnheim, N. (2003) Huntington disease expansion mutations in humans can occur before meiosis is completed. Proc. Natl. Acad. Sci. 100:8834-8.
., .. (2002). Tiemann-Boege I, Navidi W, Grewal R, Cohn D, Eskenazi B, Wyrobek AJ, Arnheim N. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Proc Natl Acad Sci U S A. [ 2002 ] Nov 12;99(23):14952-7.
 

Honors and Awards
Endowed Chair, Ester Dornsife Chair in Biological Sciences, 1998-5/31/2008  
USC Distinguished Professor, Distinguished Professor of Biological Sciences, Molecular Biology, and Biochemistry, 2001  
 
 
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