Assignment of the gene for human arylsulfatase B, ARSB, to chromosome region 5p11----5qter

The structural gene coding for human arylsulfatase B, ARSB, is assigned to 5p11----5qter by analysis of somatic cell hybrids isolated from two separate fusions of human fibroblasts carrying a translocation involving chromosome 5 with the Chinese hamster cell line a3.     

Assignment of the human 8.5 H gene to chromosome 5, region 5q35

The human 8.5 H probe was isolated from a human cerebellum cDNA library with a probe corresponding to the coding region of the murine 8.5 M cDNA. This cDNA isolated from a murine cDNA library constructed from newborn cerebral hemispheres was selected because of its strong expression in embryonic neurons. Consequently the corresponding human gene could be a candidate for hereditary neurodegenerative diseases. The human 8.5 H gene was assigned by somatic hybrid analysis to chromosome 5; this chromosome contains the gene(s) for spinal muscular atrophy (SMA), a group of heritable degenerative diseases that selectively affect the anterior horn motor neuron of the spinal cord. The localization by in situ hybridation of 8.5 H on 5q35 excluded the possibility that this gene is identical to SMA. The SMA gene(s) was (were) known, from linkage analysis, to be in a region (5q11.2-q13.3) very distant from 5q35.     

Assignment of the human gene for phosphoglycolate phosphatase to chromosome 16

Summary Seventeen independently derived primary mouse-human hybrid clones were scored for the expression of human phosphoglycolate phosphatase (PGP) by electrophoresis and for the presence of human chromosomes with the aid of Q banding. The correlation of biochemical and cytogenetic analyses shows that the segregation of human PGP in these hybrids is concordant only with human chromosome 16, thus enabling the assignment of the genetic locus for PGP to human chromosome 16.     

Assignment of the human gene for histidine-rich glycoprotein to chromosome 3

Histidine-rich glycoprotein (HRG) is a monomeric plasma glycoprotein involved in the modulation of coagulation and fibrinolysis. Using Southern analysis of human-rodent somatic cell hybrid DNA with a human HRG-specific cDNA probe, the HRG gene was assigned to chromosome 3. One hybrid that was known to contain only a segment of chromosome 3 also reacted positively with the HRG probe. Hybridization analysis with a set of chromosome 3-specific probes showed that the segment of chromosome 3 present in this hybrid is missing the region pter-p14, which indicates that HRG is not located in this region. No restriction fragment length polymorphisms were detected for HRG with 10 commonly used restriction enzymes.     

Assignment of the gene for acetylcholinesterase to distal mouse chromosome 5.

Characterization of genomic clones encoding mouse acetylcholinesterase enabled us to identify a restriction fragment length polymorphism that distinguishes between the progenitor strains for the recombinant inbred strain sets AKXD and BXD. The strain distribution pattern for this polymorphism indicates that Ache is located on distal mouse chromosome 5.     

Assignment of the alpha B-crystallin gene to human chromosome 11

Using a human alpha B-crystallin genomic probe and human-mouse somatic cell hybrids, the human alpha B-gene was assigned to chromosome 11 and further corroborated by in situ hybridization to normal metaphase chromosomes. This assignment confirmed and regionally mapped the locus to q22.3-23.1.     

Assignment of the human tyrosine aminotransferase gene to chromosome 16

Summary The liver enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5) catalyzes the rate-limiting step in the catabolic pathway of tyrosine. Deficiency in TAT enzyme activity underlies the autosomally inherited disorder tyrosinemia II (Richner-Hanhart syndrome). Using a human TAT cDNA clone as hybridization probe, we have determined the chromosomal location of the TAT structural gene by Southern blot analysis of DNAs from a series of human x rodent somatic cell hybrids. The results assign the TAT gene to human chromosome 16.     

Assignment of the structural gene coding for albumin to human chromosome 4

Summary Albumin is a developmentally regulated serum protein synthesized in the liver mainly during adulthood. Family studies using variant forms of albumin established autosomal linkage between albumin and group-specific component protein (GS). Since GC has been assigned to human chromosome 4, albumin can be indirectly assigned to the same chromosome; however no direct assignment has been made. Recently, the human albumin cDNA probe has been isolated and characterized. It thus permits a direct chromosomal assignment of the albumin gene in the human genome. When the cDNA probe was hybridized to the HindIII digested total human DNA, an intense band at 6.8 kb was present. When the probe was hybridized to the HindIII digested Chinese hamster CHO-K1 DNA, a less intense band at 3.5 kb was found, plus three other faint bands. When the probe was hybridized to a series of human/CHO-K1 cell hybrids retaining a complete hamster genome and various combinations of human chromosomes, it was evident that hybrids containing human albumin gene sequences could be readily distinguished from hybrids containing no human albumin gene. Analysis of 22 primary cell hybrids for the presence or absence of human albumin sequences has assigned the albumin gene to human chromosome 4. Similar results were obtained using another restriction endonuclease EcoR1. Thus, by direct assay of the genomic albumin gene sequences in the cell hybrids, we provide evidence for a direct assignment of the structural gene for human albumin to chromosome 4.     

Assignment of the human fibronectin structural gene to chromosome 2

A cloned human cDNA probe for fibronectin (FN) containing 1.3 kb of the human FN coding region has been used to determine the chromosome that encodes the structural gene in human-mouse somatic cell hybrids. The results show that human chromosome 2 encodes the FN structural gene.     

Assignment of the gene for acid beta-glucosidase to human chromosome 1.

The structural gene for human acid beta-glucosidase (GBA) has been assigned to chromosome 1 using somatic cell hybridization techniques for gene mapping. The human enzyme was detected in mouse RAG cell-human fibroblast cell hybrids by a sensitive double antibody immunoprecipitation assay using a mouse antihuman GBA antibody. No cross-reactivity between mouse beta-glucosidase and human GBA or neutral beta-glucosidase (GBN) was observed. Fifty-two primary, secondary, and tertiary manmouse hybrid lines, derived from three separate fusion experiments, were analyzed for human GBA and enzyme markers for the human chromosomes. Without exception, the presence of human GBA in these hybrid clones was correlated with the presence of human chromosome 1 or its enzymatic markers, phosphoglucomutase 1 (PGM1), and fumarate hydratase (FH). All other human chromosomes were eliminated by the independent segregation of GBA and their respective enzyme markers and/or chromosomes. Using a RAG X human fibroblast line with a mouse-human rearrangement of human chromosome 1, the locus for GBA was limited to the region 1p11 to 1qter.     

Assignment of the human parathyroid hormone gene to chromosome 11

Summary A panel of human-mouse and human-Chinese hamster cell hybrid DNA's was screened for hybridisation with a fragment of the human parathyroid hormone chromosomal gene. A 7-kilobasepair Msp I restriction fragment homologous to this probe was found to segregate with the human chromosome 11.     

Assignment of the human cytochrome c1 gene to chromosome 8

We previously isolated a cDNA clone for human cytochrome c1. The insert DNA of approximately 950 bp from this clone was used as a probe to identify the cytochrome c1 gene. High molecular weight DNAs extracted from a panel of 14 independent human-mouse somatic cell hybrids were digested with BamHI and analyzed by Southern blot hybridization. The results indicated that the gene for human cytochrome c1 is located on chromosome 8.     

Assignment of the human glycogen debrancher gene to chromosome 1p21

Glycogen debranching enzyme is a monomeric protein containing two independent catalytic activities of glycantransferase and glucosidase that are both required for glycogen degradation. Its deficiency causes type III glycogen storage disease. A majority of the patients with this disease have deficient enzyme activity in both liver and muscle (type IIIa) but approximately 15% of them lack enzyme activity only in the liver (type IIIb); however, the enzyme is a monomer and appears to be identical in all the tissues. The cDNA coding for the complete human muscle debranching enzyme has recently been isolated. Using the cDNA clones, the debrancher gene was localized to human chromosome 1 by somatic cell hybrid analysis. Regional assignment to chromosome band 1p21 was determined by in situ hybridization. Mapping of the debrancher gene to a single chromosome site is consistent with our hypotheses that a single gene encodes both liver and muscle debrancher protein.     

Assignment of the human dihydrofolate reductase gene to the q11----q22 region of chromosome 5.

Cells from a dihydrofolate reductase-deficient Chinese hamster ovary cell line were hybridized to human fetal skin fibroblast cells. Nineteen dihydrofolate reductase-positive hybrid clones were isolated and characterized. Cytogenetic and biochemical analyses of these clones have shown that the human dihydrofolate reductase (DHFR) gene is located on chromosome 5. Three of these hybrid cell lines contained different terminal deletions of chromosome 5. An analysis of the breakpoints of these deletions has demonstrated that the DHFR gene resides in the q11----q22 region.     

Assignment of the gene coding for human catalase to the short arm of chromosome 11

Human and murine catalases can be separated electrophoretically as single bands of different mobility. In man-mouse somatic cell hybrids, however, detection of human catalase is precluded by the complexity of banding patterns resulting from interference of a catalase-modifying enzyme activity. We have identified human catalase in hybrid clones by Laurel electrophoresis employing a specific anti-human catalase antibody, and by exploiting heat stability differences. Catalase co-segregates with LDH A and is probably located on the short arm of chromosome 11.     

Assignment of a structural gene for beta-glucuronidase to human chromosome C7.

An electrophoretic technique was developed which allows the separation of human beta-glucuronidase (GUS EC 3.2.1.3.1) from the enzyme present in cultured murine. Chinese and Syrian hamster cells in one buffer system on Cellogel. Using this technique a number of independent human-mouse somatic cell hybrids have been analyzed for the segregation of GUS, other enzyme markers, and all human chromosomes. The results indicate that a structural gene for human beta-glucuronidase is located on chromosome C7.     

Assignment of the porcine loci for MYOD1 to chromosome 2 and MYF5 to chromosome 5

Porcine-specific polymerase chain reaction (PCR) and a pig–rodent somatic cell hybrid panel were used to map two members of the MyoD gene family. MYOD1 was assigned to pig chromosome 2 and MYF5 to chromosome 5.