Abstract

Severe Combined Immunodeficiency Disease (SCID) is an autosomal recessive mutation that occurs in Athabascan speaking Indians (Navajo and Apache) at a frequency of approximately 2%. The incidence of SCID in Navajo babies is 1:2000 live births.
The specific aim of this study is to map the """"""""Navajo SCID"""""""" recessive gene by using genetic linkage, looking for coinheritance of the SCID gene with a DNA marker of known chromosomal location. To accomplish this, we will use a collection of highly polymorphic DNA markers including CA repeat microsatellite markers throughout the human genome. To date, we have over 200 DNA markers, including 80+ variable number tandem repeats (VNTR) and 125 CA repeat microsatellite marker. To study inheritance, we have assembled a collection of DNA preparations from 16 different Navajo kindreds. This includes 17 affected children and a total of 78 family members. The affected sample population is growing at approximately two kindreds per year. The DNA samples will be typed using the DNA probes and microsatellite markers. These data will be analyzed to find linkage between a mapped probe and the SCID gene. We plan to use the linkage information for prenatal diagnosis of affected fetuses and carrier detection of unaffected relatives. Eventually, we plan to identify and characterize the gene which causes SCID in this native American population and understand its role in regulating immune function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI028339-01A2
Application #
3142785
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1993-09-30
Project End
1996-06-30
Budget Start
1993-09-30
Budget End
1994-06-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Xiao, Tony Z; Singh, Kanal; Dunn, Elizabeth et al. (2012) T cell and B Cell immunity can be reconstituted with mismatched hematopoietic stem cell transplantation without alkylator therapy in artemis-deficient mice using anti-natural killer cell antibody and photochemically treated sensitized donor T cells. Biol Blood Marrow Transplant 18:200-9
Xiao, Zheng; Dunn, Elizabeth; Singh, Kanal et al. (2009) A non-leaky Artemis-deficient mouse that accurately models the human severe combined immune deficiency phenotype, including resistance to hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 15:1-11
Povirk, Lawrence F; Zhou, Tong; Zhou, Ruizhe et al. (2007) Processing of 3'-phosphoglycolate-terminated DNA double strand breaks by Artemis nuclease. J Biol Chem 282:3547-58
Li, Lanying; Salido, Eduardo; Zhou, Yungui et al. (2005) Targeted disruption of the Artemis murine counterpart results in SCID and defective V(D)J recombination that is partially corrected with bone marrow transplantation. J Immunol 174:2420-8
Wang, Junhua; Pluth, Janice M; Cooper, Priscilla K et al. (2005) Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression. DNA Repair (Amst) 4:556-70
Li, Lanying; Moshous, Despina; Zhou, Yungui et al. (2002) A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. J Immunol 168:6323-9
Li, Lanying; Zhou, Yungui; Wang, Junhua et al. (2002) Prenatal diagnosis and carrier detection for Athabascan severe combined immunodeficiency disease. Prenat Diagn 22:763-8
O'Marcaigh, A S; DeSantes, K; Hu, D et al. (2001) Bone marrow transplantation for T-B- severe combined immunodeficiency disease in Athabascan-speaking native Americans. Bone Marrow Transplant 27:703-9
Denianke, K S; Frieden, I J; Cowan, M J et al. (2001) Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study. Bone Marrow Transplant 28:227-33
Moshous, D; Li, L; Chasseval, R et al. (2000) A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p. Hum Mol Genet 9:583-8

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