Pamela R. Fain, Ph.D.
Population and quantitative genetics with an emphasis on autoimmune
diseases
The primary emphasis of the research program is in the genetics of type 1 diabetes and other autoimmune disorders; but there are also collaborative projects that relate to cancer genetics. The current focus is on identifying IDDM17, a diabetes susceptibility gene that maps to human chromosome 10q25.1. IDDM17 was mapped by genetic linkage studies in a large Bedouin Arab family (Verge et al, 1998). Progress is being made towards positional cloning IDDM17 by linkage disequilibrium mapping and the use of bioinformatics resources. Over 40 single nucleotide polymorphisms (SNPs) have been identified in the 125 kb candidate region by direct sequencing of family members. A specific diabetogenic haplotype has emerged from these studies, but the gene corresponding to IDDM17 remains to be found. Characterization of the SNPs in Caucasian populations is an important goal that awaits the development of laboratory techniques for efficient SNP typing as part of work in progress. Another objective is to evaluate the predictive value of IDDM17, HLA typing, and autoantibody testing in determining who will have type 1 diabetes, not only in the Bedouin Arab family, but also in Caucasian populations and families. A related research objective is to determine the extent to which genes within or near the MHC explain the association between type 1 diabetes and other autoimmune diseases, with a focus on type 1 diabetes and Addison’s disease.
The research program also involves many collaborations in the area of disease gene mapping and positional cloning of Mendelian and complex phenotypes, including primarily genetic linkage studies of lung cancer and other smoking-related diseases as part of the national Genetic Epidemiology of Lung Cancer Consortium, studies of congenital heart disease, and studies of modifier genes in polycystic kidney disease.
Publications
Verge CF, Vardi P, Babu S, Bao F, Erlich HA, Bugawan T, Yu L, Eisenbarth GS, Fain PR: Oligogenic inheritance of type 1a diabetes in a large Bedouin Arab family. J. Clin. Invest. 102:1569-1575, 1998.
Sangthongpitag K, Moore KR, Lapsys NM, Bao F, Babu S, Fain PR, Verge CF: No linkage of apoptosis antigen 1 (APO-1 or Fas) with type 1 diabetes. Human Heredity 48:343-345, 1998.
Kawasaki E, Noble J, Erlich H, Mulgrew C, Fain PR, Eisenbarth GS: Transmission of DQ haplotypes to patients with type 1 diabetes. Diabetes 47:1971-73, 1998.
Bennett CL, Yoshioka R, Kiyosawa HK, Barker DF, Fain PR, Shigeoka AO,
Chance PF: An X-linked syndrome of polyendocrinopathy, immune dysfunction
and diarrhea (XPID) maps to Xp11.23-Xq13.3. Am J Hum Genet 66:461-8, 2000.
Fain PR, Eisenbarth GS: Type 1 diabetes, autoimmunity, and the MHC. In
Lowe W (ed): Genetics of Diabetes Mellitus. Norwell: Kluwer Academic Publishers,
2001.
Redondo M, Fain PR, Eisenbarth GS: Genetics of type I diabetes. In Means
A (ed). Genetics of Diabetes Mellitus. Recent Progress in Hormone Research,
The Endocrine Society, 2001.
Fain PR, Kimberling WJ, Stetler G, Roberts C, Johnson A, Wu G, Morrow
S, Robinson ML: Mutations found in PKD1 by DHPLC analysis. Am J Hum Genet
69 (Suppl):577, 2001.
Mestroni L, Taylor MRG, Robinson M, Brodsky GL, Moss A, Goodnight JL,
Sinagra G, Di Lenarda A, Fain P: Comprehensive mutational analysis of
the Lamin A/C gene in familial and sporadic dilated cardiomyopathies.
Am J Hum Genet 69 (Suppl): 605, 2001.
Robinson ML, Wu G, Babu S, Roberts C, Bao F, Fain PR: Genotyping single
nucleotide polymorphisms in four different amplicons in diabetes. Am J
Hum Genet 69 (Suppl):577, 2001.
Robles DT, Fain PR, Eisenbarth GS: The genetics of autoimmune polyendocrine
syndrome type II. In Eisenbarth GS (ed). Endocrinology and Metabolism
Clinics of North America. W.B. Saunders Co., 31:353-68, vi-vii 2002.
Fain PR, Eisenbarth GE: Genetics of type 1a diabetes. In Baxter J, Melmed
S, New M, Martini L (eds): Genetics in Endocrinology. Philadelphia: Lippincott-Raven
Publishers, pp. 37-72, 2002.
Alkhateeb A, Stetler GL, Old W, Talbert J, Uhlhorn C, Taylor M, Fox A,
Miller C, Dills DG, Ridgway C, Bennett DC, Fain PR, Spritz RA. Mapping
of an autoimmunity susceptibility locus (AIS1) to chromosome 1p31.3-p32.2.
Hum Mole Genet 11:661-667, 2002.
Gottlieb PA, Fain PR: The genetic basis of autoimmune adrenal deficiency.
Curr Opin Endocrinol and Diabetes, 9:237-243, 2002.
Pacheco TR, Bellus GA, Oreskovich NM, Talbert J, Old W, Fain PR: Exclusion
of Candidate Genes and Loci for Multiple Lentigines syndrome. J Invest
Dermatol 119:535-8, 2002.
Bao F, Babu SR, Bobenhausen I, Robles DT, Canniff JD, Sikela J, Fain PR,
Eisenbarth GS: Single nucleotide polymorphism studies of IDDM 17 in Bedouin
Arab and American families from the Human Biological Data Interchange
(HBDI). Diabetes 51 (Suppl 2):A155, 2002.
Gottlieb PA, Yu L, Babu SR, Wang T, Fain PR: Genetic and phenotypic heterogeneity
in Addison’s disease and type 1 diabetes. Diabetes 51 (Suppl 2):
A554, 2002.
Babu SR, Bao F, Roberts CM, Old W, Gowan K, Eisenbarth GS, Fain PR: Caspase
7 is a positional candidate gene for IDDM17 in a Bedouin Arab family.
Diabetes 51 (Suppl 2): A547, 2002.
Park Y, Sanjeevi CB, Robles D, Yu L, Rewers M, Gottlieb PA, Fain P, Eisenbarth
GS: HLA genotypes (Class II, MIC-A, D6S273): Additional association of
intra-MHC genes with Addison’s disease risk. Tissue Antigens, 60(2):155-63,
2002.
Taylor MRG, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E,
Di Lenarda A, Bohlmeyer TJ, Ferguson DA, Brodsky GL, Boucek, MM, Lascor
J, Moss, Li WP, Stetler GL, Spritz RA, Muntoni F, Bristow MR, Mestroni
L and the Familial Dilated Cardiomyopathy Registry Research Group. Natural
History of Dilated Cardiomyopathy Due to Lamin A/C Gene Mutations. J Am
Coll Cardiol, 41:771-780, 2003.
Miller YE, Fain PR. Genetic susceptibility to lung cancer. In Ianuzzi
C (ed). Genetics of Pulmonary Disorders, Sem Resp Critical Care Med, 24:197-204,
2003.
Alkhateeb, A, Fain, PR, Thody, A, Bennett, DC, and Spritz, RA. Epidemiology
of vitiligo and associated autoimmune diseases in Caucasian probands and
their families. Pigment Cell Res, 16:208-214, 2003.
Fain, PR, Gowan, K, LaBerge, GS, Alkhateeb, A, Stetler, GS, Talbert, J,
Bennett, DC, and Spritz, RA. A Genomewide Screen for Autoimmune Vitiligo:
Confirmation of AIS1 on Chromosome 1p31 and Evidence for Additional Susceptibility
Loci. Am J Hum Genet, 72:1560-4, 2003.
Melanitou E, Fain PR, Eisenbarth GS: Genetics of type 1A (immune-mediated)
diabetes. J Autoimmunity, 21:93-98, 2003.
Conant GC, Plimptom SJ, Old W, Wagner A, Fain PR, Pacheco TR, Heffelfinger.
Parallel Genehunter: Implementation of a Linkage Analysis Package for
Distributed-Memory Architectures J Parallel Distrib Comput, 63:674-782,
2003.
Babu SR, Bao F, Roberts CM, Martin AK, Gowan K, Eisenbarth GS, Fain PR:
Caspase 7 is a positional candidate gene for IDDM17 in a Bedouin Arab
family. Ann NY Acad Sci, 1005:340-343, 2003.
Bao F, Babu S, Roberts CM, Martin AK, Gowan K, Eisenbarth GS, Fain PR:
Single nucleotide polymorphism study of IDDM17 in Bedouin Arab family.
Ann NY Acad Sci, 1005:348-351, 2003.
Spritz R, Fain P, Bennett D. IL-36 The Epidemiology and Genetics of Generalized
Vitiligo. Pigment Cell Res 16:589-590, 2003.
Spritz RA, Gowan K, Bennett DC, Fain PR. Novel vitiligo susceptibility
loci on chromosomes 7 (AIS2) and 8 (AIS3), confirmation of SLEV1 on chromosome
17, and their roles in an autoimmune diathesis. Am J Hum Genet 74:188-191,
2004.
Pacheco TR, Oreskovich N, Fain PR: Genetic heterogeneity in the multiple
lentigines/LEOPARD/Noonan syndromes. Am J Med Genet 127A:324-326, 2004.
Bailey-Wilson JE, Amos CI, Pinney S, Petersen GM, de Andrade M, Wiest
JS, Fain P, Schwartz AG, You M, Franklin W, Klein C, Gazdar A, Rothschild
H, Mandal D, Coons T, Slusser J, Lee J, Gaba C, Kupert E, Perez A, Zhou
X, Zeng D, Liu Q, Zhang Q, Seminara D, Minna J, Anderson M: A major lung
cancer susceptibility locus maps to chromosome 6q23-25. Am J Hum Genet
75:460-74, 2004.
McNair WP, Ku L, Taylor MRG, Fain PR, Dao D, Wolfel E, Mestroni L: A SCN5A
mutation associated with dilated cardiomyopathy, conduction disorder and
arrhythmia. Circulation 110:2163-2167, 2004.
Barker JM, Ide A, Hostetler C, Yu L, Miao D, Fain PR, Eisenbarth GS, Gottlieb
PA: Endocrine and immunogenetic testing in individuals with type 1 diabetes
and 21-hydroxylase autoantibodies: Addison’s disease in a high risk
population. J Clin Endo Metab, in press, 2004.
Redondo MJ, Fain PR, Krischer, J, Yu L, Cuthberston D, Eisenbarth GS:
Expression of beta-cell autoimmunity does not differ between dizygotic
twins and siblings of patients with type 1 diabetes. J Autoimmun, in press
.
Fain PR, McFann KK, Taylor MRG, Tison, M, Johnson AM, Reed, B, Schrier
RW: Modifier genes play a significant role in the expression of PKD1.
Kidney Intl, in press, 2004.
