Localization of the human progesterone receptor gene to chromosome 11q22–q23

Summary The human progesterone receptor gene was mapped by in situ hybridization using two cDNA probes corresponding to the 5′ and 3′ part of the coding sequence. This gene was localized to 11q22-q23.     

Human zinc finger gene ZNF23 (Kox16) maps to a zinc finger gene cluster on chromosome 16q22, and ZNF32 (Kox30) to chromosome region 10q23-–q24

Two members of the KOX gene family, ZNF23 (KOX16) and ZNF32 (KOX30), have been mapped by in situ hybridization to chromosome regions 16q22 and 10q23-q24, respectively. The map location of ZNF23 and ZNF32 placed these zinc finger protein genes near to chromosome loci that, under certain in vitro conditions, are expressed as fragile sites (FRA16B, FRA16C) and (FRA10D, FRA10A, FRA10B and FRA10E). Human zinc finger gene ZNF32 maps to a chromosome region on 10q23-24 in which deletions have been observed associated with malignant lymphoma on 10q22-23 and with carcinoma of the prostate on 10q24. ZNF23 is located on 16q22 in a chromosomal region that has been involved in chromosome alterations characteristic of acute myeloid leukemia. A second Kox zinc finger gene (ZNF19/KOX12) was recently mapped to the same chromosome region on human chromosome 16q22. In the analogous murine position, the murine zinc finger genes Zfp-1 and Zfp-4 are found in the syntenic 16q region of mouse chromosome 8. Thus, ZNF19 and ZNF23 might be members of an evolutionarily conserved zinc finger gene cluster located on human chromosome 16q22.     

Regional chromosomal localisation of APOA2 to 1q21–1q23

Summary Using in situ hybridisation, we have mapped APOA2 to the 1q21–1q23 region of chromosome 1. DNA hybridisation to somatic cell hybrids made from cells carrying a balanced translocation between X and 1 confirms the localisation as proximal to 1q23. This was further confirmed by the presence of two polymorphic alleles in a cell line carrying a deletion of 1q25–1q32.     

Pure monosomy and trisomy 2q24.2→q3105 due to an inv ins(7;2)(q21.2;q3105q24.2) segregating in four generations

Summary An inv ins(7;2)(q21.2;q3105q24.2) was found to segregate through four generations of a family. Adjacent-1 segregation aneusomies were ascertained in five patients: three monosomics and two trisomics; and the corresponding syndromes were delineated. The comparative analysis between these and other previously described 2q aneusomic individuals led to the conclusion that a large cleft between first and second toes is a constant feature in monosomy 2q24q31. No other trait could plausible be mapped. Risks of 7.9 to 31.9% for aneusomic children and of 26.3% for abortion were estimated in the present family.     

Interaction between the ribosomal subunits: 16S rRNA suppressors of the lethal ΔA1916 mutation in the 23S rRNA of <Emphasis Type="Italic">Escherichia coli</Emphasis>

A1916 in 23S rRNA is located in one of the major intersubunit bridges of the 70S ribosome. Deletion of A1916 disrupts the intersubunit bridge B2a, promotes misreading of the genetic code and is lethal. In a genetic selection for suppressor mutations, two base substitutions in 16S rRNA were recovered that restored viability and also allowed expression of ΔA1916-associated capreomycin resistance. These mutations were G1048A in helix 34 and U1471C in helix 44. Restoration of function is incomplete, however, and the double mutants are slow-growing, defective in subunit association and support high levels of translational errors. In contrast, none of these parameters is affected by the single 16S suppressor mutations. U1471C likely affects another intersubunit contact, bridge B6, suggesting that interactions between different bridges and cross-talk between subunits contributes to ribosomal function.     

Construction of a porcine YAC library and mapping of the cardiac muscle ryanodine receptor gene to Chromosome 14q22–q23

Large-scale physical mapping of the porcine genome has been limited because up to now no suitable genomic libraries for this purpose have been available. Therefore, we have constructed a yeast artificial chromosome (YAC) library from porcine lymphocytes. The library was cloned in the amplifiable vector pCGS966. A total of 10080 YAC clones was obtained and has been ordered into 105 96-well microtiter plates. An average insert size of 300 kb was calculated from the analysis of 78 randomly selected clones, giving a onefold coverage of the porcine genome. To analyze the complexity, we have screened the library for five different genes and isolated four different clones containing parts of three of these genes. One YAC clone harboring parts of the porcine cardiac muscle ryanodine receptor (RYR2) gene allowed us to assign this locus to Chromosome (Chr) 14q22-q23. The data were confirmed by PCR analysis of a rodent-porcine hybrid cell panel.     

Molecular characterization of a patient with del(1)(q23–q25)

Summary We report a patient (S.T.) with multiple congenital anomalies and developmental delay associated with an interstitial deletion of 1q23–1q25. Molecular analysis of the deletion was performed using DNA markers that map to 1q. Five DNA markers, MLAJ-1 (D1S61), CRI-L1054 (D1S42), HBI40 (D1S66), OS-6 (D1S75), and BH516 (D1S110), were demonstrated to be deleted. Informative polymorphisms demonstrated this to be a de novo deletion of the maternally derived chromosome. Deletion status was determined using restriction fragment length polymorphism (RFLP) analysis supplemented with densitometry in the experiments where RFLP analysis was not fully informative. Deletions were confirmed by Southern analysis using genomic DNA from a somatic cell hybrid retaining the del(1)(q23–q25) chromosome that was constructed from patient S.T. Flow karyotyping confirmed the deletion and estimated that the deletion encompassed 11,000–16,000 kb. The clinical and cytogenetic characteristics of S.T. are compared with those of ten previously described patients with monosomy 1q21–1q25.     

Genetic aberration in primary hepatocellular carcinoma：correlation between p53 gene mutation and loss—of—heterozygosity on chromosome 16q21—q23 and 9p21—p23

To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC),we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9,16 and 17.Loss-of-heterozygosity(LOH) is observed with high frequency on chromosomal region 17p13(36k/55,65%),9q21-p23(28/55,51%),16q21-23(27/55,49%) in tumors.Meanwhile,microsatellite instability is rarely found in these microsatellite loci.Direct sequencing was performed to detect the tentative mutation of tumor wuppressor genes in these regions:p53,MTS1/p16,and CDH1/E-cadherin.Wihin exon 5-9 of p53 gene,14 out of 55 HCC specimens(24%) have somatic mutations,and nucleotide deletion of this gene is reported in HCC for the first time.Mutation in MTS1/p16 is found only in one tumor case.We do not find mutations in CDH1/E-cadherin.Furthermore,a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23,which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.     

Localization of the human c-kit protooncogene on the q11–q12 region of chromosome 4

Summary Using a 166-nucleotide-long DNA synthetic probe corresponding to the v-kit sequence (1458-1623), we have mapped the human c-kit gene to chromosome 4 at the q11–q12 band by in situ hybridization on chromosomes from human lymphocyte preparations.     

Rapid Identification of <Emphasis Type="Italic">Lactobacillus</Emphasis><Emphasis Type="Italic">acidophilus</Emphasis> by Restriction Analysis of the 16S–23S rRNA Intergenic Spacer Region and Flanking 23S rRNA Gene

A rapid molecular approach was developed for the initial identification of Lactobacillus acidophilus strains which are difficult to identify using a single biochemical test. The 16S–23S rRNA intergenic spacer regions and flanking 23S rRNA genes of 19 strains of lactobacilli were amplified and the nucleotide sequences and restriction site polymorphisms were analyzed. AluI was the most useful of the restriction enzymes analyzed and produced reproducible digestion profiles in the L. helveticus, L. plantarum, and L. casei groups, as well as in L. acidophilus. This restriction fragment length polymorphism method may be useful for the identification of L. acidophilus strains in dairy products.     

Sequence studies on the soybean chloroplast 16S–23S rDNA spacer region

The sequence of the ribosomal spacer region of soybean chloroplast DNA including the 3 end of the 16S rRNA gene, the tRNA^Ala and tRNA^Ile genes (but not their introns), the three intergenic regions and the 5 end of the 23S rRNA gene, has been determined. This sequence has been compared to corresponding regions of other angiosperm chloroplast DNAs. Secondary structure models are proposed for the entirety of the intergenic regions a, b and c and for the flanking rRNA regions. A model for a common secondary structure of the ribosomal spacer intergenic regions from chloroplasts of higher plants is proposed, which is supported by comparative evidence.     

16S–23S rRNA Intergenic Spacer Region Variability in the Genus Frankia

16S–23S rRNA internally transcribed spacer (ITS) sequences from 53 Frankia strains were sequenced and sized from polymerase chain reaction amplification products and compiled with 14 selected 16S–23S ITS sequences from public database. Frankia genomes included two to three ITS copies lacking length polymorphism except for nine strains. No tRNA gene was encountered in this region. Frankia strains exhibited various lengths (369 to 452 nt) and a wide range of sequence similarity (35–100%) in the ITS region. The average pairwise distance varied from 0.368 (clusters 1 and 2) to 0.964 (clusters 3 and 4) and was 0.397, 0.138, 0.129, and 0.016, respectively, for cluster 4 (saprophytic non-infective/non-effective), clusters 1 and 3 (facultative symbiotic), and cluster 2 (obligate symbiotic). This suggests a gradual erosion of Frankia diversity concomitantly with a shift from saprophytic non-infective/non-effective to facultative and symbiotic lifestyle. Comparative sequence analyses of the 16S–23S rRNA intergenic spacer region of Frankia strains are not useful to assign them to their respective cluster or host infection group. Accurate assignment required the inclusion of the adjacent 16S and 23S rRNA gene fragments.     

Assignment of the gene for human tenascin to the region q32–q34 of chromosome 9

Summary Tenascin (TN) is a hexameric extracellular matrix glycoprotein that is highly expressed in solid tumors but has a restricted distribution in normal adult tissues. Each TN subunit is composed of segments with high homology to the sequences of epidermal growth factor, fibronectin and fibrinogen. Furthermore, it has been suggested that TN could modulate epithelial-mesenchymal and neuronal-glial interactions. Here, using a cDNA probe to human TN, we have carried out Southern blot analysis of the genomic DNAs from a panel of human-hamster somatic cell hybrids carrying different complements of human chromosomes. The results demonstrate that the human TN gene is located on chromosome 9. Furthermore, in situ hybridization studies demonstrate that human TN is located at 9q32–q34.     

Microsatellite genotyping of Chromosome 14q13.2-14q13 in the vicinity of proteasomal gene<Emphasis Type="Italic"> PSMA6</Emphasis> and association with Graves’ disease in the Latvian population

The 270-kb Chromosome 14q13.2-14q13 region harboring the proteasomal alpha subunit 6 gene PSMA6 was analyzed for polymorphism of five microsatellite repeats in cases/controls and association with Graves disease. Four novel microsatellite markers were localized to the 14q13.2 region upstream of PSMA6. Dinucleotide repeats HSMS801, HSMS702, HSMS701 were identified in two introns of the gene KIAA0391; the most upstream trinucleotide HSMS602 marker was found in an intron of the C14orf24 gene. A polymorphism study performed on the Latvian population revealed 13 and 14 alleles for HSMS801 and HSMS702, respectively, seven alleles for HSMS701, and four alleles for HSMS602. Heterozygosity analysis revealed that all the four markers obey Hardy-Weinberg distribution. The previously described HSMS006 marker, represented by 12 alleles, is localized in intron 6 of the PSMA6 gene. No significant differences were observed between patients and controls in allele distribution of the HSMS702 and HSMS701 microsatellite repeats. However, the allele frequencies of HSMS006 and HSMS801 were significantly different between Graves disease and control subjects. The 181- and 185-bp alleles of HSMS006 and the 133-, 143-, and 149-bp alleles of HSMS801 were found more often, but the 189- and 191-bp alleles of HSMS006 were much less frequent in Graves disease patients compared with the controls. An additional 174-bp allele of the HSMS602 marker, absent in healthy subjects, was found in Graves disease patients.     

Does the fetal genotype affect maternal physiology during pregnancy?

Conventional wisdom states that associations between fetal growth and diseases in pregnancy, such as pregnancy-induced hypertension (PIH) and gestational diabetes (GDM), result from effects of the mother's genotype or environment acting on her physiology which subsequently affect the fetus. However, recent evidence from human mothers carrying macrosomic offspring with Beckwith Wiedemann syndrome and pregnant mice carrying p57(kip2)-null offspring suggest that variation in the fetal genome can modify maternal physiology to increase fetal nutrient delivery and optimise growth. These are some of the first documented examples of such effects, whereby the genome of one individual directly affects the physiology of another related individual from the same species. We propose that this mechanism is involved in the aetiology of PIH and GDM.     

Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1 → q22.3 in a patient with tyrosinemia type II

Summary Tyrosinemia II is an autosomal-recessively inherited condition caused by deficiency in the liver-specific enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5). We have restudied a patient with typical symptoms of tyrosinemia II who in addition suffers from multiple congenital anomalies including severe mental retardation. Southern blot analysis using a human TAT cDNA probe revealed a complete deletion of both TAT alleles in the patient. Molecular and cytogenetic analysis of the patient and his family showed one deletion to be maternally inherited, extending over at least 27 kb and including the complete TAT structural gene, whereas loss of the second TAT allele results from a small de novo interstitial deletion, del 16 (pterq22.1::q22.3qter), in the paternally inherited chromosome 16. Three additional loci previously assigned to 16q22 were studied in our patient: haptoglobin (HP), lecithin: cholesterol acyltransferase (LCAT), and the metallothionein gene cluster MT1, MT2. Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome.     

An antiboy antibody? Re-examination of the maternal immune hypothesis

The maternal immune hypothesis (MIH) argues same sex attraction (SSA) results from maternal immune attack on fetal male-specific brain structures and involves the previous biological influence of elder brothers. One of the surveys supporting this is shown to be based on an unsuitable sample and to contain some strong contrary evidence. The hypothesis relies on at least four speculative ideas and there is evidence against each. (1) Likely immune response prevalence is too low compared with calculated SSA prevalence resulting from the fraternal birth order effect. (2) Testis immune attack would be more likely than brain attack but is not known. (3) Fetal brain structures are practically indistinguishable at birth and subsequent brain anatomical gender differentiation only occurs after birth when no attack is occurring. (4) The hypothesis also predicts unfavourable biology for late birth-order males but in fact the reverse is generally true, and neurological effects are very minor. Studies show aborted fetuses caused by likely maternal immune attack are predominantly girls rather than boys, which also argues against the theory. Studies on identical twins show that common factors such as uterine environment are only a small influence on SSA and post-natal idiosyncratic reactions and non-shared environmental factors are much larger influences.     

10q(q23→qter) duplication: GOTs,HK1, and other gene markers

Summary Gene marker analyses have been carried out in a patient with 10q(q23qter) duplication. The observed elevation of red cell glutamic oxaloacetic transaminase activity is compatible with earlier somatic cell hybridization studies that mapped the locus to this region. Hexokinase-1 activity in the red cells was normal, which is consistent with its prior assignment to the unaffected part of chromosome 10 (10pterq23).