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A physical map linking the five CD1 human thymocyte differentiation antigen genes
1Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
Insights
Researchers mapped the five human CD1 genes on chromosome 1. They determined the precise order and spacing of these genes within the CD1 complex using advanced molecular techniques.
Area of Science:
- Immunogenetics
- Molecular Biology
Background:
- Human CD1 molecules are cell surface glycoproteins involved in immune responses.
- They are structurally related to MHC class I and II molecules but encoded by independent genes.
- Five human CD1 genes (CD1A, -B, -C, -D, -E) have been identified, with functions of CD1D and CD1E products yet to be fully elucidated.
Purpose of the Study:
- To physically map and characterize the organization of the human CD1 gene cluster.
- To determine the order and inter-gene distances within the CD1 locus on chromosome 1.
Main Methods:
- Pulse field gel electrophoresis
- Cosmid cloning
- DNA walking techniques
Main Results:
- Established tight linkage of all five human CD1 genes.
- Spanned 190 kb of DNA containing the entire CD1 gene complex using 14 overlapping cosmids.
- Determined the gene order as CD1D-CD1A-CD1C-CD1B-CD1E.
- Found that most CD1 genes share the same transcriptional orientation, with a larger intergenic distance between CD1D and CD1A.
Conclusions:
- The human CD1 gene family is tightly clustered on chromosome 1.
- Detailed physical mapping provides a framework for further functional studies of CD1 genes and their products.
Abstract:
Human CD1 is a family of thymocyte differentiation antigens which consist of heavy chains with mol. wts between 43 and 49 kd binding to beta 2 microglobulin. They are distant relatives of the major histocompatibility complex (MHC) class I and II products. Five human CD1 genes have been described. Three (CD1A, -B and -C) code for the serologically defined CD1a, -b and -c antigens. The protein products of the other two genes, CD1D and CD1E, remain unknown. All CD1 genes are located on chromosome 1 and hence are independent of the MHC locus. In this paper, the tight linkage of the CD1 genes has been established by pulse field gel electrophoresis, cosmid cloning and walking techniques. The 190 kb of DNA linking all five CD1 genes has been spanned by 14 overlapping cosmids. The order of the genes in the CD1 complex is CD1D-CD1A-CD1C-CD1B-CD1E, and, with the exception of CD1B, they are arranged in the same transcriptional orientation. The genes are evenly spaced in the complex except for the distance between CD1D and CD1A, which is two to three times greater than the average.