Alternative titles; symbols
This entry does not represent an expressed gene. It is included here mainly for historical purposes, since D14S1 was the first RFLP to be identified (after the DNA polymorphism discovered by Kan and Dozy (1978)).
Botstein et al. (1980) suggested that variation in nucleotide sequences resulting in variation in cleavage by site-specific endonucleases ('restriction enzymes') are sufficiently frequent in the human genome as to be highly useful as markers in chromosome mapping. They suggested the designation restriction fragment length polymorphism (acronym, RFLP, pronounced 'rif-lip'). To be useful, the polymorphism should be in a single-copy sequence. A collection of 150-200 such polymorphisms distributed over the genome would have the potential for greatly enhancing the power of family linkage studies. Disorders of reduced penetrance and multifactorial causation might be amenable to genetic analysis. The HpaI polymorphism (143020) in a noncoding segment on the 3-prime flank of the beta-globin gene was the first to be found, by Kan and Dozy (1978). Polymorphism was then defined in the noncoding part of the gamma-globin genes (142200). Before the paper of Botstein et al. (1980), Solomon and Bodmer (1979) had suggested the usefulness of restriction polymorphisms as markers in linkage studies.
Wyman and White (1980) found a human DNA segment (which they referred to as 'a locus') that was the site of restriction fragment length polymorphism. The polymorphism was found by hybridizing a 16-kilobase-pair segment of single-copy human DNA, selected from the human genome library cloned by Maniatis's group (Lawn et al., 1978) in lambda phage Charon 4A, to a Southern transfer of total human DNA digested with EcoRI. The 'locus' was found to be highly variable with a potential usefulness in linkage studies exceeded only by HLA (White, 1981). Family studies supported mendelian inheritance. Studies by somatic cell hybridization assigned the 'locus' to chromosome 14 (White, 1981). Terminology tentatively suggested was 'arbitrary restriction polymorphism' (ARP), with numbers in sequence of discovery. 'Anonymous' might be substituted for 'arbitrary.' It seemed desirable for the designation to include the chromosomal site (and such should be determined as early as possible). When more than one such polymorphism was assigned to one chromosome, a letter can be used following the chromosome number. According to this convention, the polymorphism described by Wyman and White (1980) was designated ARP-14A, or simply ARP-14, until another on that chromosome was found. The symbol adopted at HGM6 (Oslo) called for D (for DNA), then the chromosome number, then S for segment, and 1 for the first such identified on chromosome 14: D14S1. De Martinville et al. (1982) assigned the polymorphism to chromosome 14 in the q21-qter region. At least 8 alleles were demonstrated. Balazs et al. (1982) concluded that D14S1 maps to the subtelomeric region of 14q, 14q32, in close proximity to the IGH-CG1 locus (Kirsch et al., 1982). The conclusion was based on 3 independent lines of evidence: gene dosage, somatic cell hybrid studies, and pedigree analysis. It is probably significant that the highly polymorphic D14S1 'locus' is in the same region where much somatic rearrangement goes on during differentiation of immunoglobulin-producing B lymphocytes, specifically in 'class switch', and where the break occurs in the generation of de novo translocations in lymphatic malignancies. GM73 and GM74 (otherwise known as KOP) were used in the gene dosage studies and in cell hybrid studies. (KOP cell lines, carrying an X;14 translocation, were used by Ricciuti and Ruddle (1973) in the mapping of X-chromosome loci.) They studied 13 pedigrees segregating for Gm variants at the gamma-1 locus. A recombination fraction of 3.1%, with a 90% fiducial limit for the upper recombination value of 11.5%, was found. The data were consistent with the generally held estimate that one unit of meiotic recombination corresponds to about 1 million basepairs. By in situ hybridization, Donlon et al. (1983) assigned D14S1 to 14q32.1-q32.2.
Balazs, I., Purrello, M., Rubinstein, P., Alhadeff, B., Siniscalco, M. Highly polymorphic DNA site D14S1 maps to the region of Burkitt lymphoma translocation and is closely linked to the heavy chain gamma-1 locus. Proc. Nat. Acad. Sci. 79: 7395-7399, 1982. [PubMed: 6818543] [Full Text: https://doi.org/10.1073/pnas.79.23.7395]
Botstein, D., White, R. L., Skolnick, M., Davis, R. M. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32: 314-331, 1980. [PubMed: 6247908]
de Martinville, B., Wyman, A. R., White, R., Francke, U. Assignment of the first random restriction fragment length polymorphism (RFLP) locus (D14S1) to a region of human chromosome 14. Am. J. Hum. Genet. 34: 216-226, 1982. [PubMed: 6280496]
Donlon, T. A., Litt, M., Newcom, S. R., Magenis, R. E. Localization of the restriction fragment length polymorphism D14S1 (pAW-101) to chromosome 14q32.1-32.2 by in situ hybridization. Am. J. Hum. Genet. 35: 1097-1106, 1983. [PubMed: 6650497]
Kan, Y. W., Dozy, A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc. Nat. Acad. Sci. 75: 5631-5635, 1978. [PubMed: 281713] [Full Text: https://doi.org/10.1073/pnas.75.11.5631]
Kirsch, I. R., Morton, C. C., Nakahara, K., Leder, P. Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science 216: 301-303, 1982. [PubMed: 6801764] [Full Text: https://doi.org/10.1126/science.6801764]
Lawn, R. W., Fritsch, E. F., Parker, R. C., Blake, G., Maniatis, T. The isolation and characterization of linked alpha- and beta-globin genes from a cloned library of human DNA. Cell 15: 1157-1174, 1978. [PubMed: 728996] [Full Text: https://doi.org/10.1016/0092-8674(78)90043-0]
Ricciuti, F. C., Ruddle, F. H. Assignment of three gene loci (PGK, HGPRT, G6PD) to the long arm of the human X chromosome by somatic cell genetics. Genetics 74: 661-678, 1973. [PubMed: 4750811] [Full Text: https://doi.org/10.1093/genetics/74.4.661]
Solomon, E., Bodmer, W. F. Evolution of sickle variant gene. (Letter) Lancet 313: 923 only, 1979. Note: Originally Volume I. [PubMed: 86686] [Full Text: https://doi.org/10.1016/s0140-6736(79)91398-9]
White, R. L. Personal Communication. Salt Lake City, Utah 3/30/1981.
Wyman, A. R., White, R. A highly polymorphic locus in human DNA. Proc. Nat. Acad. Sci. 77: 6754-6758, 1980. [PubMed: 6935681] [Full Text: https://doi.org/10.1073/pnas.77.11.6754]