Confirmation of the regional localization of the genes for human acid alpha-glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization

We have confirmed the localization of human acid alpha-glucosidase ( GAA ) to 17q21 → q25 and of adenosine deaminase ( ADA ) to 20q13 → 20qter by examination of hybrid clones derived from a fusion between a human cell line carrying a 17/20 balanced translocation (17pter → 17q25:: 20q13 → 20qter; 20pter → 20q13:: 17g25 → 17gter) and a mouse line deficient in thymidine kinase. These hybrids were constantly maintained in HAT selective media in order to select for the presence of the human thymidine kinase gene on the intact chromosome 17 (17q21 → 22) or the 17/20 (17pter → 17q25:: 20q13 → 20qter) translocation chromosome. We detected human GAA by rocket immunoelectrophoresis, using a heterologous antibody raised against human acid alpha-glucosidase. A clone which contained the 17/20 translocation and no intact chromosome 17 was still positive for GAA. This finding confirms the exclusion of GAA from 17q25 -0 17qter reported by Nickel et al . (1982). Combined with earlier results (Weil et al . 1979), GAA can be assigned to 17q21 → 17q25. A clone which contained only the 17/20 translocation chromosome and no intact chromosome 20 contained ADA. This confirms the previous localization of ADA to 20q13.2 → qter by gene dosage studies (Philip et al . 1980).     

The assignment of the human gene coding for complement C5 to chromosome 9q22-9q33.

The presence or absence of the human gene for the fifth component of complement (C5) was analysed in 19 human-rodent hybrid cell lines by hybridization to a radiolabelled probe derived from a human C5 cDNA clone. The segregation of C5 in these hybrids suggested that the gene is localized on chromosome 9, in the region 9q21-9qter. In situ hybridization refined the assignment of C5 to chromosome 9q22-33.     

Family studies on nucleoside phosphorylase and the short arm of chromosome 14

A family with two nucleoside phosphorylase-deficient patients has been scored for the segregation of NP⁰ and the variable region 14p. The most likely 14p: NP recombination fraction is (M5 in males and 0–30 in females.
There is no family data to assign the Pi:Gm linkage group to chromosome 14, but as immunoglobulin heavy chain has been assigned to this chromosome by somatic cell methods the most likely gene order is 14p:NP: Pi:Gm with Pi in 14q2 and Gm in 14(q23 →q32), but the order 14p:NP:Gm:Pi with Pi in 14(q24 → qter) and Gm in 14(q22 → q24) is not excluded.
The available linkage data between biochemical markers on acrocentric chromosomes and their short arm markers suggest that there may be more recombination towards the ends of human chromosomes whether or not those ends carry centromeres.     

The human type II collagen gene (COL2A1) assigned to 12q14.3

A cosmid clone containing the entire human type II α1 collagen gene ( COL2A1 ) was used as probe in the Southern analysis of DNA from a panel of human/hamster somatic cell hybrids containing different portions of human chromosome 12. Two of the hybrids exhibited a similar terminal deletion q14.3→qter, but one was positive for the gene while the other was negative. Therefore, the gene must reside in the region q14.3.     

Assignment of the human gene for peptidase E to the chromosomal region 17q23 → 17qter

Peptidase E has been studied in 16 independent human-Syrian hamster hybrids and 16 subclones. Evidence is presented indicating that the human gene for Peptidase E is on chromosome 17 in the region 17q23 → 17qter.     

Localization of the human aryl hydrocarbon hydroxylase gene to the 2q31→2pter region of chromosome 2

Analysis of hybrid cells containing fragments of human chromosome 2 has resulted in the regional localization of a gene for aryl hydrocarbon hydroxylase (AHH). Hybrids prepared from a human cell line containing an established translocation have shown that AHH can be localized to the region 2q31→2pter.     

Confirmation of the assignment of human biliverdin reductase to chromosome 7

Segregation of biliverdin reductase (BLVR) in 11 independent human-mouse hybrids confirms the assignment to chromosome 7 in man and gives a regional localization of 7pter → 7q22. Isoelectric focusing of BLVR reveals genetically determined variation among inbred strains of mice.     

A cytochrome P-450 gene family mapped to human chromosome 19

We have recently isolated a cloned cDNA coding for a cytochrome P-450 of human liver microsomal membranes, which corresponds to a major phenobarbital-inducible cytochrome P-450 of rat liver. This human cytochrome P-450 is encoded by a member of a multigene family. DNA extracted from a panel of 12 independent human-rodent somatic cell hybrids was analysed by Southern blot hybridization with the cloned cDNA. The results indicate that all components of this cytochrome P-450 gene family are located on chromosome 19. Evidence from hybrids derived from an individual carrying a balanced translocation suggests a regional localization of 19p13.2→qter. Analysis of human metaphase chromosomes by in situ hybridization localizes this cytochrome P-450 gene family further to the long arm of chromosome 19 in the region q13.1→qter. We propose the designation P450PB for this locus.     

The Human RNA Helicase A (DDX9) Gene Maps to the Prostate Cancer Susceptibility Locus at Chromosome Band 1q25 and Its Pseudogene (DDX9P) to 13q22, Respectively

RNA helicase A is the homolog of the Drosophila maleless protein, an essential factor involved in dosage compensation, and plays a crucial role in early development in mammals. Here, we have mapped the human RNA helicase A (DDX9) gene to the major susceptibility locus for prostate cancer at chromosome band 1q25, and its pseudogene (DDX9P) to the band 13q22 by fluorescence in situ hybridization, somatic cell hybrid analysis, and assignment of YAC clones, respectively.     

Molecular cytogenetic studies of duplication 9q32→q34.3 inserted into 9q13

Fluorescence in situ hybridization (FISH) studies using whole chromosome 9 painting probe, classical satellite (9q12-specific) probe and abl cosmid probe (locus: 9q34) were performed on a female infant who was born with multiple congenital anomalies and the karyotype 46,XX, 9q+. The results of FISH confirm the euchromatic nature of the extra material on the long arm of chromosome 9, and provide evidence that it is of chromosome 9 origin. The structural rearrangement has probably resulted from an insertion of a duplicated segment 9q32→q34.3 into band q13, as shown by the abl cosmid probe. The clinical features in this patient are similar to the previously reported cases of partial trisomy 9q3.     

利用辐射杂种板(GB4)精细定位人类新基因H-RalGDS于染色体9q34.1

目的 Ｈ－ＲａｌＧＤＳ基因是我们新近分离与克隆的人类新的Ｒａｓ相关基因,是鼠Ｒａｌ鸟嘌呤核苷酸解离刺激因子（ＲａｌＧＤＳ）在人类的同源基因。利用辐射杂种板（ｒａｄｉａｔｉｏｎ ｈｙｂｒｉｄ,ＲＨ）制图法进行该基因的精细定位。方法 根据Ｈ－ＲａｌＧＤＳ基因ｃＤＮＡ的３’不翻译区设计正反向引物,ＰＣＲ扩增人／鼠辐射体细胞杂种板（ｒａｄｉａｔｉｏｎ ｈｙｂｒｉｄ Ｇｅｎｂｒｉｄｇｅ ４ ｐａｎｅｌ）,并     

Two unrelated children with distal long arm deletion of chromosome 7: clinical features, cytogenetic and gene marker studies

Two phenotypically abnormal, unrelated children with deletion of the distal segment of 7q (7q32→pter) are described. In one instance the mother was the carrier of a balanced translocation between chromosomes 6 and 7, and in the second case the deletion was a de novo event. Their phenotypes were compared to previously reported cases and found to have many non-specific clinical features in common. Gene marker studies for some of the genes tentatively localized to chromosome 7 showed no anomalous segregation. The Hageman coagulation factor (Factor XII) activity in bath probands was normal, and hetero-zygosity for alleles of the Kidd blood group in the first proband excludes assignment of the Kidd locus to the distal portion of chromosome 7q.     

Regional localization of a human cytochrome P-450 (CYP1) to chromosome 19q 13.1–13.3

A phenobarbitone inducible cytochrome P-450 gene family ( CYP1 ) has recently been localized to chromosome 19q13.1-qter. We have used a human liver cDNA probe in in situ hybridization experiments to metaphase chromosomes from two balanced translocation carriers, 46, XX, t(11;19) (q13;q13.1) and 46, XX, t(7;19) (q31.3;q13.3) to obtain a more precise localization. The results suggest a regional assignment for CYP1 to chromosome 19q13.1–13.3.     

Omphalocele in trisomy 3q: further delineation of phenotype

We report a case of a patient with omphalocele, dysmorphic features, and mild developmental delay associated with a chromosomal aberration. Chromosome studies showed that the propositus carries a maternally derived unbalanced translocation der(4)t(3;4)(q27.3;q32.3), resulting in trisomy for region 3q27.3→qter and monosomy for 4q32.3→qter. Because the association between dup3q and omphalocele has been reported in several cases, we analyzed the data on 93 previously reported patients with partial trisomy of the long arm of chromosome 3 and compared the clinical features between the cases. The imbalance of chromosome 3 in the patient was further defined by fluorescence in situ hybridization (FISH) studies using bacterial artificial chromosome (BAC) clones. BAC clone RP11-171N2 was identified as a breakpoint-spanning clone in the patient and his mother. Based on our comparative analysis, we have delineated that the smallest region of overlap (SRO) associated with omphalocele is from BAC 171N2 to 3qter. We hypothesize that the SRO contains a gene(s) important in normal abdominal wall development and is of potential interest for further investigation.     

Functional complementation in mouse -- human radiation hybrids assigns the putative murine scid gene to the pericentric region of human chromosome 8

Fragments of human chromosome 8 were introduced into cells derivedfrom murine scid mice via X-Irradiation and somatic cell fusion.The resulting hybrid clones contained human DNA fragment(s)which complemented the hyper-radlosensitivity of the scid cells.Alu-PCR products from these hybrids were used for chromosomepainting using the technique of chromosome in situ suppressionhybridization, allowing assignment of the human HYRC (hyper-radlosensitivityof murine scid mutation, complementing) gene, a candidate fora V(D)J recombinase gene, to human chromosome 8q11.     

A recognizable phenotype in a child with partial duplication 13q in a family with t(10q;13q)

A case of partial duplication 13q14 → qter is reported in a 9-year-old male with clinical symptoms which include trigonocephaly and synophrys, producing an easily identifiable phenotype. The chromosome duplication resulted from a familial t(10;13)(qter;q14). Subsequently, a normal balanced carrier sibling was diagnosed prenatally.     

CD28/CTLA-4 ligands: the gene encoding CD86 (B70/B7.2) maps to the same region as CD80 (B7/B7.1) gene in human chromosome 3q13-q23

CD86 (B70/B7.2) is an antigen of the immunoglobulin superfamily expressed on monocytes, dendritic cells and activated B,T, and natural killer cells. CD86 was recently identified as a second ligand for the T cell antigens CD28 and CTLA-4, and plays an important role in the co-stimulation of T cells in a primary immune response. We report here the assignment of the CD86 gene to human chromosome 3 using Southern blot analysis on a panel of hamster × human somatic cell hybrid genomic DNA. Fluorescence hybridization in situ on metaphase chromosomes coupled with GTG banding (G-bands by trypsin using Giemsa staining) confirmed this assignment and localized the CD86 gene to 3q13-q23 region. The CD86 gene is, therefore, located in the proximity of the CD80 (B7/B7.1) gene, the first identified ligand for CD28 and CTLA-4, previously mapped to chromosome 3q13.3-q21. Deletions, inversions and insertions of chromosome 3q21-q26, as well as translocations of 3q21 with other chromosomes have been described in many cases of acute myeloid leukemia (AML), acute nonlymphocytic leukemia (ANLL), chronic myeloid leukemia (CML) and myelodisplastic syndromes (MDS), suggesting that this region contains several genes involved in the leukemic process.     

De novo 46,XX, dir dup (11)(q13.3→q14.2) in a patient with mental retardation, congenital cardiopathy and thrombopenia

A 31-year-old female is reported with mild to moderate mental retardation, facial dysmorphy, congenital cardiopathy, and mild thrombocytopenia as the most important clinical findings. Chromosome analysis in lymphocytes showed a de novo dir dup (11)(q13.3→14.2), by both G-banding and FISH techniques. Previously reported constitutional duplications of 11q are mostly the result of unbalanced translocations involving chromosome 11q, and are associated with a partial monosomy or trisomy of the translocation partner chromosome. In case of an unbalanced translocation it is not clear which clinical findings result from the chromosome 11 duplication and which result from the abnormality on the translocation partner chromosome. This is the first report on a constitutional duplication of chromosome region 11q13.3→14.2 without involvement of other chromosomes.     

Confirmation that the Type I collagen gene on chromosome 17 is COL1A1 (α1(I)), using a human genomic probe

A cloned 15 kb genomic fragment from the human α1 (I) collagen gene (COL1A1) has been used as a probe on restriction digests of DNA from human-mouse somatic cell hybrids. Positive results on hybrids containing chromosome 17 as their only karyotypically visible human material confirm the assignment of this gene to chromosome 17. Hybrids which contain fragments of chromosome 17 are used to confirm the localization to 17q21-qter.