Mark Leppert
Professor and Co-Chair of Human Genetics
B.A. Wesleyan University
Ph.D. University of Minnesota
Research
Contribution to Society
Providing researchers throughout the worldwide genomic community
with access to genetic markers and techniques for rapid, large-scale
genotyping efforts will contribute to rapid advances in the identification
of genes associated with diseases in humans. In turn, these discoveries
will lead to new preventions and treatments for inherited disorders.
Research Summary
An aim of our research group is to develop new and improved techniques
for identifying genetic variations that confer predispositions
to human disorders and traits. The ascertainment of families in
which such variant genes are segregating is an important first
step toward localizing the disease-related genes on specific chromosomes.
The genealogical resources available at the University of Utah
have enabled researchers in human genetics to identify extended
families who can contribute such information. Localization of
a variant gene predisposing to a disease is accomplished by finding
a marker allele that is inherited along with the disease phenotype.
However, as many common diseases in humans are complex in their
phenotypic expression, and as several genes may be involved, often large numbers of related
individuals have to be genotyped at many marker loci. This requirement
has led our group to adapt technologies evolving from DNA sequence
research to the problem of large-scale and rapid genotyping. We
are using this genetic approach, coupled with positional cloning,
to understand inherited forms of epilepsy, particularly a specific
type in which intermittent seizures appear at birth and cease
spontaneously within six months, and to understand inherited forms
of macular degeneration, a common form of retinal eye disease.
Unprecedented efforts aimed at extensive phenotyping of Utah families
as part of the Utah Genetic Reference Project have yielded successful
progress toward identifying the genetic loci responsible for quantitative
traits such as phenylthiocarbamide sensitivity and variation in
levels of lymphocyte subpopulations. These same families were
utilized for the construction of the haplotype map for the International
HapMap Project, which will readily facilitate the discovery of
allelic variants responsible for common diseases.
References
1. Leppert MF, Singh NA (2003) NONSYNDROMIC SEIZURE DISORDERS: Epilepsy and the Use of the Internet to Advance Research. Ann Rev Genom Sep 2003, Vol. 4, pp. 437-457
2. Malhotra A, Peiffer AP, Ryujin DT, Elsner T, Kanner RE, Leppert MF, Hasstedt SJ (2003) Further evidence for the role of genes on chr2 and chr5 in the inheritance of pulmonary function. Am J Respir Crit Care Med. Jun 5 [Epub ahead of print]
3. Sandovici I, Leppert M, Hawk PR, Suarez A, Linares Y, Sapienza C (2003) Familial aggregation of abnormal methylation of parental alleles at the IGF2/H19 and IGF2R differentially methylated regions. Hum Mol Genet. Jul 1;12 (13):1569-1578
4. Drayna D, Coon H, Kim UK, Elsner T, Cromer K, Otterud B, Baird L, Peiffer AP, Leppert M (2003) Genetic analysis of a complex trait in the Utah Genetic Reference Project: A major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p Hum Genet. May;112(5-6):567-72
5. Hall MA, Norman PJ, Thiel B, Tiwari H, Peiffer A, Vaughan RW, Prescott S, Leppert M, Schork NJ, Lanchbury JS (2002) Quantitative trait loci on chromosomes 1, 2, 3, 4, 8, 9, 11, 12 and 18 control variation in levels of T and B lymphocyte sub-populations. Am J Hum Genet. May;70(5):1172-82
6. Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D (2003) Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science Feb 21;299(5610):1221-5
7. Coon H, Eckfeldt JH, Leppert MF, Myers RH, Arnett DK, Heiss G, Province MA, Hunt SC (2002) A genome-wide screen reveals evidence for a locus on chromosome 11 influencing variation in LDL cholesterol in the NHLBI Family Heart Study. Hum Genet. Sep;111(3):263-269
8. Warren EH, Otterud BE, Linterman RW, Brickner AG, Engelhard VH, Leppert MF, Martin PJ, Riddell SR (2002) Feasibility of using genetic linkage analysis to identify the genes encoding T cell-defined minor histocompatibility antigens. Tissue Antigens. Apr;59(4):293-303
9. Hunt SC, Ellison RC, Atwood LD, Pankow JS, Province MA, Leppert MF (2002) Genome scans for blood pressure and hypertension: the NHLBI Family Heart Study. Hypertension. Jul;40(1):1-6
10. Samowitz WS, Curtin K, Ma KN, Edwards S, Schaffer D, Leppert MF, Slattery ML (2002) Prognostic significance of p53 mutations in colon cancer at the population level. Int J Cancer. Jun 1;99(4):597-602
11. Bernstein PS, Leppert MF, Singh N, Dean M, Lewis RA, Lupski JR, Allikmets R, Seddon JM (2002) Genotype–phenotype analysis of ABCR variants in macular degeneration probands and siblings. Invest Ophthalmol Vis Sci. Feb;43(2):466-473
12. Swoboda KJ, Soong BW, McKenna C, Brunt ER, Litt M, Bale JF Jr, Ashizawa T, Bennet LB, Bowcock AM, Roach ES, Gerson D, Matsuura T, Heydemann PT, Nespeca MP, Jankovic J, Leppert MF, Ptacek LJ (2001) Paroxysmal dyskinesia and infantile convulsions. Clinical and linkage studies. Genes Chromosomes Cancer. Dec;32(4):381-383
