Linkage analysis and physical mapping near the gene for x-linked agammaglobulinemia at Xq22

Journal Article · Mon Feb 01 00:00:00 EST 1993 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1993.1066· OSTI ID:6660303

Parolini, O; Lassiter, G L; Henry, M J; Conley, M E ^[1]; Hejtmancik, J F ^[2]; Allen, R C; Belmont, J W ^[3]; Barker, D F ^[4]

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1. Univ. of Tennessee College of Medicine, Memphis (United States) St. Jude Children's Research Hospital, Memphis, TN (United States)
2. National Inst. of Health, Bethesda, MD (United States)
3. Baylor College of Medicine, Houston, TX (United States)
4. Univ. of Utah, Salt Lake City (United States)

The gene for x-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the prob p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, and 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segman of DNA within which the gene for SLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DCS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XL)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel. Our studies also limit the segment of DNA within which the XLA gene must lie to the 3- to 4-cM distance between DCS442 and DXS94 and they identify and orient polymorphisms that can be used in genetic counseling not only for XLA but also for Pelizaeus-Merzbacher disease (PLP deficiency), Alport syndrome (COL4A5 deficiency), and Fabry disease ([alpha]-galactosidase A difficiency). 31 refs., 5 figs., 2 tabs.

• OSTI ID: 6660303
• Journal Information: Genomics; (United States), Vol. 15:2; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLOBULINS-GAMMA
HEREDITARY DISEASES
HUMAN X CHROMOSOME
GENETIC MAPPING
CHROMOSOMES
DNA
ELECTROPHORESIS
PROBES
WOMEN
ANIMALS
DISEASES
FEMALES
GLOBULINS
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
MAMMALS
MAN
MAPPING
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
VERTEBRATES
X CHROMOSOME
550400* - Genetics