RESUMO
We report the case of a boy whose karyotype at birth showed additional material on one chromosome 15. He underwent treatment for unilateral nephroblastoma at 6 years old. At 23 years old, he presented with body asymmetry, facial dysmorphism, arachnodactyly, severe scoliosis, and mental retardation. Molecular cytogenetic analyses of peripheral lymphocytes demonstrated a complex mosaic with three clones. A major cell lineage (68%) showed a chromosome 15 with additional material fused to its telomere long arm that was constituted by an inverted duplicated 15q24.3-qter segment. Therefore, the resulting add(15)(q) harbored an intrachromosomal triplication with the middle segment being inverted in orientation. A minor cell lineage (7%) showed an abnormal chromosome 3 resulting from a telomeric fusion between its short arm and an inverted duplicated 15q24.3-qter segment. The third cell lineage (25%) showed a normal 46,XY constitution. Finally, this resulted in tetrasomy for the distal 15q24.3-qter region in 75% of the patient's lymphocytes. To our knowledge, distal 15q tetrasomy is rare and only eight cases have been reported in the literature, all due to a supernumerary analphoid marker consisting of an inverted duplication. We report here the first observation of distal 15q tetrasomy associated with a 46 chromosomes constitution. We compare the phenotype of our patient to previous cases of distal tetrasomy 15q and discuss the mechanisms underlying this chromosomal rearrangement.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 15/genética , Anormalidades Múltiplas/patologia , Adulto , Criança , Bandeamento Cromossômico , Face/anormalidades , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Deficiência Intelectual/patologia , Cariotipagem , Masculino , Mosaicismo , Fenótipo , Escoliose/patologia , Tumor de Wilms/patologiaAssuntos
Blefaroptose/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 2/genética , Predisposição Genética para Doença , Oftalmoplegia/genética , Translocação Genética , Criança , Mapeamento Cromossômico , Segregação de Cromossomos , Feminino , Fibrose , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/patologia , Oftalmoplegia/congênito , Oftalmoplegia/patologia , LinhagemRESUMO
We report the case of a girl presenting with an unusual form of multiple joint fusion. Skeletal abnormalities consisted of radioulnar synostosis and vertebral fusions without any carpal, digital or tarsal involvement, and broad ribs and clavicles. Spinal X-rays were available from age 4 to 21, demonstrating that the spinal involvement was progressive and led to a complete anterior and lateral fusion of vertebrae. A complete sequencing of the NOGGIN gene failed to find any mutation. In addition, this girl was carrier of an apparently balanced reciprocal translocation t(10;20)(p11;p13). We investigated the role of the BMP2A gene as a potential candidate gene. Fluorescence in situ hybridization with YAC probes from chromosome 20 showed that the BMP2A gene was not disrupted by the translocation breakpoint.
Assuntos
Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 20/genética , Coluna Vertebral/anormalidades , Translocação Genética , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Proteínas Morfogenéticas Ósseas/genética , Proteínas de Transporte , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Seguimentos , Transtornos do Crescimento/patologia , Humanos , Hibridização in Situ Fluorescente , Fenótipo , Fatores de TempoRESUMO
BACKGROUND: Complete deletion of the complete AZFc interval of the Y chromosome is the most common known genetic cause of human male infertility. Two partial AZFc deletions (gr/gr and b1/b3) that remove some copies of all AZFc genes have recently been identified in infertile and fertile populations, and an association study indicates that the resulting gene dose reduction represents a risk factor for spermatogenic failure. METHODS: To determine the incidence of various partial AZFc deletions and their effect on fertility, we combined quantitative and qualitative analyses of the AZFc interval at the DAZ and CDY1 loci in 300 infertile men and 399 control men. RESULTS: We detected 34 partial AZFc deletions (32 gr/gr deletions), arising from at least 19 independent deletion events, and found gr/gr deletion in 6% of infertile and 3.5% of control men (p>0.05). Our data provide evidence for two large AZFc inversion polymorphisms, and for relative hot and cold spots of unequal crossing over within the blocks of homology that mediate gr/gr deletion. Using SFVs (sequence family variants), we discriminate DAZ1/2, DAZ3/4, CDY1a (proximal), and CDY1b (distal) and define four types of DAZ-CDY1 gr/gr deletion. CONCLUSIONS: The only deletion type to show an association with infertility was DAZ3/4-CDY1a (p = 0.042), suggesting that most gr/gr deletions are neutral variants. We see a stronger association, however, between loss of the CDY1a SFV and infertility (p = 0.002). Thus, loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility.
Assuntos
Cromossomos Humanos Y/genética , Deleção de Genes , Proteínas Nucleares/genética , Oligospermia/genética , Proteínas de Ligação a RNA/genética , Sequência de Bases , Inversão Cromossômica , Cromossomos Humanos Y/química , Proteína 1 Suprimida em Azoospermia , Conversão Gênica , Dosagem de Genes , Predisposição Genética para Doença , Variação Genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Polimorfismo Genético , Recombinação GenéticaRESUMO
BACKGROUND: Mental retardation (MR) affects 2-3% of the human population and some of these cases are genetically determined. Although several genes responsible for MR have been identified, many cases have still not been explained. METHODS: We have identified a pericentric inversion of the X chromosome inv(X)(p22.3;q13.2) segregating in a family where two male carriers have severe MR while female carriers are not affected. RESULTS: The molecular characterisation of this inversion led us to identify two new genes which are disrupted by the breakpoints: KIAA2022 in Xq13.2 and P2RY8 in Xp22.3. These genes were not previously fully characterised in humans. KIAA2022 encodes a protein which lacks significant homology to any other known protein and is highly expressed in the brain. P2RY8 is a member of the purine nucleotide G-protein coupled receptor gene family. It is located in the pseudo-autosomal region of the X chromosome and is not expressed in brain. CONCLUSIONS: Because the haploinsufficiency of P2RY8 in carrier mothers does not have a phenotypic consequence, we propose that the severe MR of the affected males in this family is due to the absence of the KIAA2022 gene product. However, screening 20 probands from X linked MR families did not reveal mutations in KIAA2022. Nonetheless, the high expression of this gene in fetal brain and in the adult cerebral cortex could be consistent with a role in brain development and/or cognitive function.
Assuntos
Encéfalo/metabolismo , Cromossomos Humanos X/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Adulto , Linhagem Celular , Criança , Pré-Escolar , Quebra Cromossômica/genética , Inversão Cromossômica/genética , Clonagem Molecular , Mecanismo Genético de Compensação de Dose , Feminino , Testes Genéticos , Heterozigoto , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Cariotipagem , Masculino , Especificidade de Órgãos , Análise de Sequência de DNAAssuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 20/genética , Telômero/genética , Adolescente , Adulto , Criança , Pré-Escolar , Deleção Cromossômica , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Transtornos Mentais/patologia , Monossomia , Cromossomos em Anel , Translocação GenéticaRESUMO
During meiosis in male mammals, the X and Y chromosomes become heterochromatic and transcriptionally silent, and form the XY body. Although the HP1 proteins are known to be involved in the packaging of chromosomal DNA into repressive heterochromatin domains, their involvement in facultative heterochromatinization has not been precisely determined. Here, we analyse, for the first time in humans, the subcellular distribution of the heterochromatin protein HP1alpha, HP1beta and HP1gamma isoforms, in male pachytene spermatocytes, and the XY body facultative heterochromatin in particular. Our results demonstrate that HP1beta and HP1gamma, but not the HP1alpha isoforms, decorate the entire XY body in half the pachytene nuclei observed. In some nuclei, the XY body appears to be only partially labelled. In these cases, the HP1beta and HP1gamma signals are adjacent to the Yq12 constitutive heterochromatin and signal appears to originate in this region before spreading over the entire XY body. This distribution suggests that HP1beta and HP1gamma proteins, which are components of the constitutive heterochromatin, may also be involved in the facultative heterochromatinization of the XY body. Nevertheless, their absence from the early pachytene substage, even though the XY body is already condensed, suggests that these proteins are not involved in the initiation of this process.
Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Cromossomos Humanos X/metabolismo , Cromossomos Humanos Y/metabolismo , Meiose/fisiologia , Anticorpos/metabolismo , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/imunologia , Humanos , Masculino , Espermatócitos/citologiaRESUMO
Non-syndromic X linked mental retardation (MRX) is a heterogeneous group of conditions in which all patients have mental retardation as the only constant phenotypic feature. We have identified a female patient with mental retardation and a balanced translocation involving chromosomes X and 21, t(X;21)(p11.2;q22.3). Physical mapping of the translocation breakpoint on the human X chromosome was performed using fluorescence in situ hybridisation. We have mapped the X chromosome breakpoint to a 21 kb DNA fragment upstream of the first exon of the KLF8 (ZNF741) gene in Xp11.21. We have subsequently shown that the KLF8 transcript is no longer detected in cells from the patient, although KLF8 expression is otherwise normally present in control lymphoblasts. Mutation screening of probands from 20 unrelated XLMR families linked to the proximal short arm of the human X chromosome failed to show any mutation in the coding region of the KLF8 gene.
Assuntos
Cromossomos Humanos Par 21/genética , Regulação da Expressão Gênica/genética , Deficiência Intelectual/genética , Translocação Genética , Cromossomo X/genética , Pré-Escolar , Feminino , Humanos , SíndromeRESUMO
Thalassaemia intermedia is a moderate form of thalassaemia resulting from various genetic defects. We report an undescribed mechanism leading to this condition: a somatic deletion of the beta-globin gene in the haemopoietic lineage of a heterozygous beta-thalassaemic patient. We did molecular studies and haemoglobin analysis of the patient and his parents. We found that the deletion gives rise to a mosaic of cells with either one or no functional beta-globin gene and it extends to a region of frequent loss of heterozygosity called LOH11A, which is located close to the beta-globin locus. Thus, loss of heterozygosity can be a cause of non-malignant genetic disease.
Assuntos
Deleção de Genes , Globinas/genética , Perda de Heterozigosidade/genética , Talassemia beta/genética , Anemia/genética , Criança , Códon sem Sentido/genética , Genes Dominantes/genética , Testes Genéticos , Genótipo , Transtornos do Crescimento/genética , Hemoglobinas/análise , Hepatomegalia/genética , Heterozigoto , Humanos , Hibridização in Situ Fluorescente , Masculino , Linhagem , Mapeamento por Restrição , Índice de Gravidade de Doença , Esplenomegalia/genética , Talassemia beta/sangue , Talassemia beta/classificação , Talassemia beta/complicaçõesRESUMO
BACKGROUND: The sequences encoding the yeast RNA polymerase II (RPB) subunits are single copy genes. RESULTS: While those characterized so far for the human (h) RPB are also unique, we show that hRPB subunit 11 (hRPB11) is encoded by a multigene family, mapping on chromosome 7 at loci p12, q11.23 and q22. We focused on two members of this family, hRPB11a and hRPB11b: the first encodes subunit hRPB11a, which represents the major RPB11 component of the mammalian RPB complex; the second generates polypeptides hRPB11balpha and hRPB11bbeta through differential splicing of its transcript and shares homologies with components of the hPMS2L multigene family related to genes involved in mismatch-repair functions (MMR). Both hRPB11a and b genes are transcribed in all human tissues tested. Using an inter-species complementation assay, we show that only hRPB11balpha is functional in yeast. In marked contrast, we found that the unique murine homolog of RPB11 gene maps on chromosome 5 (band G), and encodes a single polypeptide which is identical to subunit hRPB11a. CONCLUSIONS: The type hRPB11b gene appears to result from recent genomic recombination events in the evolution of primates, involving sequence elements related to the MMR apparatus.
RESUMO
The Sox gene family consists of several genes related by encoding a 79 amino acid DNA-binding domain known as the HMG box. This box shares strong sequence similarity to that of the testis determining protein SRY. SOX proteins are transcription factors having critical roles in the regulation of diverse developmental processes in the animal kingdom. We have characterised the human SOX7 gene and compared it to its mouse orthologue. Chromosomal mapping analyses localised mouse Sox7 on band D of mouse chromosome 14, and assigned human SOX7 in a region of shared synteny on human chromosome 8 (8p22). A detailed expression analysis was performed in both species. Sox7 mRNA was detected during embryonic development in many tissues, most abundantly in brain, heart, lung, kidney, prostate, colon and spleen, suggesting a role in their respective differentiation and development. In addition, mouse Sox7 expression was shown to parallel mouse Sox18 mRNA localisation in diverse situations. Our studies also demonstrate the presence of a functional transactivation domain in SOX7 protein C-terminus, as well as the ability of SOX7 protein to significantly reduce Wnt/beta-catenin-stimulated transcription. In view of these and other findings, we suggest different modes of action for SOX7 inside the cell including repression of Wnt signalling.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Grupo de Alta Mobilidade/metabolismo , Mapeamento Físico do Cromossomo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/fisiologia , Transativadores , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteínas de Peixe-Zebra , Sequência de Aminoácidos , Animais , Linhagem Celular , Cromossomos Humanos Par 8/genética , Clonagem Molecular , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/química , Etiquetas de Sequências Expressas , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Grupo de Alta Mobilidade/química , Humanos , Fator 1 de Ligação ao Facilitador Linfoide , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Estrutura Terciária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição SOXF , Alinhamento de Sequência , Transdução de Sinais , Sintenia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/química , Fatores de Transcrição/genética , Proteínas Wnt , beta CateninaRESUMO
The TPD52 (tumor protein D52)-like proteins are small coiled-coil motif-bearing proteins which were first identified though their expression in human breast carcinoma. TPD52-like proteins are known to interact in hetero-and homomeric fashions, but there are no known heterologous binding partners for these proteins. We now report the cloning of a novel member of the MAL proteolipid family, named MAL2, though its interaction with a TPD52L2 bait in a yeast two-hybrid screen. MAL2 is predicted to be 176 residues (19 kDa) with four transmembrane domains and is 35.8% identical to MAL, a proteolipid required in apical vesicle transport. The MAL2 prey bound all TPD52-like baits tested in the yeast two-hybrid system and in vitro translation of MAL2 produced a single 19-kDa (35)S-labeled protein which specifically bound full-length GST-Tpd52 in GST pull-down assays. The gene MAL2, which was localized to human chromosomal band 8q23 and shown to consist of four exons, is predominantly expressed in human kidney, lung, and liver. Our study has therefore identified a novel member of the MAL proteolipid family and potentially implicates TPD52-like proteins in vesicle transport.
Assuntos
Proteínas de Transporte/isolamento & purificação , Proteínas de Transporte/metabolismo , Proteínas de Membrana Transportadoras , Proteínas da Mielina , Proteínas de Neoplasias/metabolismo , Proteolipídeos/isolamento & purificação , Proteolipídeos/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Proteínas de Transporte Vesicular , Sequência de Aminoácidos , Neoplasias da Mama/química , Proteínas de Transporte/genética , Mapeamento Cromossômico/métodos , Cromossomos Humanos Par 8/genética , DNA Complementar/genética , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Dados de Sequência Molecular , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Proteínas de Neoplasias/genética , Ligação Proteica/genética , Transporte Proteico/genética , Proteolipídeos/química , Proteolipídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Células Tumorais CultivadasRESUMO
By systematic analysis of a human testis library, we have isolated the hH-Rev107-3 cDNA, identical to hH-Rev107-1 cDNA, which was previously described as a class II tumor suppressor gene. In this study, two transcripts (1 and 0.8 kb) were detected by Northern blot in all human tissues, excepted in thymus. The strongest expression was found in testis, skeletal muscle and heart. These two mRNA are probably transcribed from only one gene that we mapped to the q12-q13 region of the chromosome 11. In human testis, hH-Rev107 gene expression was localized, by in situ hybridization, within the round spermatids. To investigate a possible role for hH-Rev107 protein in testicular malignant growth, we examined the expression of this gene in germ cell tumors. A strong hH-Rev107 gene expression was observed in normal testis as well as in samples with preinvasive carcinoma in situ but was completely absent in overt tumors, both seminomas and non-seminomas. By in situ hybridization, CIS was found hH-Rev107 positive and tumor negative. A semi-quantitative assessment of hH-Rev107 mRNA level in testicular germ cell tumors, by RT-PCR, exhibited a ninefold decrease in the gene expression. No gross structural aberrations of hH-Rev107 gene were detected in these human primary tumors. The results suggest that down-regulation of hH-Rev107 may be associated with invasive progression of testicular germ cell tumors.
Assuntos
Meiose , Neoplasias Embrionárias de Células Germinativas/metabolismo , Biossíntese de Proteínas , Proteínas/genética , Espermatozoides/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Mapeamento Cromossômico , Cromossomos Humanos Par 11 , Regulação para Baixo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Dados de Sequência Molecular , Fosfolipases A2 Independentes de Cálcio , Testículo/metabolismo , Distribuição Tecidual , Proteínas Supressoras de TumorRESUMO
The mouse Vanin-1 molecule plays a role in thymic reconstitution following damage by irradiation. We recently demonstrated that it is a membrane pantetheinase (EC 3.56.1.-). This molecule is the prototypic member of a larger Vanin family encoded by at least two mouse (Vanin-1 and Vanin-3) and three human (VNN1, VNN2, VNN3) orthologous genes. We now report (1) the structural characterization of the human and mouse Vanin genes and their organization in clusters on the 6q22-24 and 10A2B1 chromosomes, respectively; (2) identification of the human VNN3 gene and the demonstration that the mouse Vanin-3 molecule is secreted by cells, and (3) that the Vanin genes encode different isoforms of the mammalian pantetheinase activity. Thus, the Vanin family represents a novel class of secreted or membrane-associated ectoenzymes. We discuss here their possible role in processes pertaining to tissue repair in the context of oxidative stress.
Assuntos
Amidoidrolases/genética , Moléculas de Adesão Celular/genética , Cromossomos Humanos Par 6/genética , Proteínas de Membrana/genética , Família Multigênica , Sequência de Aminoácidos , Animais , Sequência de Bases , Sequência Conservada , Proteínas Ligadas por GPI , Humanos , Camundongos , Dados de Sequência Molecular , Isoformas de Proteínas/genética , Homologia de Sequência de Aminoácidos , Distribuição TecidualRESUMO
The gene encoding myosin light chain kinase (MYLK) is duplicated on human chromosome 3 (HSA3; 3p13;3q21) and on a chromosome with conserved synteny to HSA3 in most non-human primate species. In human, the functional copy resides on 3q21, whereas the 3p13 site contains a pseudogene. To trace the origin of the duplication, we characterized the mouse gene Mylk. A single sequence corresponding to the functional Mylk was detected. We sequenced a 180-kb bacterial artificial chromosome clone containing the 24 first exons of Mylk; the complete mouse gene is expected to span >200 kb. Comparisons with the draft of the human genome revealed that the sequence and structure of MYLK are conserved in mammals. Fluorescence in situ hybridization (FISH) analysis indicated that the mouse gene localizes to a single site on chromosome 16B4-B5, a region with conserved synteny with HSA3q. Our study provides information on both the structure and the evolution of MYLK in mammals and suggests that it was duplicated after the divergence of rodents and primates.
Assuntos
Duplicação Gênica , Quinase de Cadeia Leve de Miosina/genética , Sequência de Aminoácidos , Animais , Bovinos , Galinhas , Mapeamento Cromossômico , Cromossomos Humanos Par 3 , Mapeamento de Sequências Contíguas , Éxons , Biblioteca Gênica , Genoma , Humanos , Hibridização in Situ Fluorescente , Íntrons , Camundongos , Camundongos Endogâmicos C57BL , Modelos Genéticos , Dados de Sequência Molecular , Pseudogenes , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass, named ABCA7. As it is the case for other ABCA genes, the predicted protein encoded by ABCA7 is a full symmetric transporter, highly conserved across species. The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors. This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Éxons/genética , Íntrons/genética , Regiões Promotoras Genéticas/genética , Transportadores de Cassetes de Ligação de ATP/química , Sequência de Aminoácidos , Animais , Linhagem Celular , Cromossomos Humanos Par 19/genética , Sequência Conservada/genética , DNA Complementar/genética , Humanos , Hibridização in Situ Fluorescente , Fígado/embriologia , Fígado/metabolismo , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos , RNA Mensageiro/análise , RNA Mensageiro/genética , Mapeamento de Híbridos Radioativos , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Baço/metabolismo , Timo/metabolismoAssuntos
Cromossomos Humanos Par 14/genética , Deficiências do Desenvolvimento/genética , Duplicação Gênica , Impressão Genômica/genética , Alelos , Pré-Escolar , Bandeamento Cromossômico , Segregação de Cromossomos/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Mães , Linhagem , Fenótipo , Polimorfismo Genético/genética , Transtornos Psicomotores/genéticaRESUMO
The human HIRA protein is encoded from a region of chromosome 22q that is critical for the DiGeorge syndrome and the velocardiofacial syndrome. We have previously reported that it directly interacts with core histones, with a novel histone-binding protein, HIRIP3, and during mouse embryogenesis, with the developmentally regulated homeodomain protein Pax3, suggesting a promoter-targeted function at the chromatin level. We here report on HIRA-interacting protein 5 (HIRIP5), a small acidic protein that interacted with HIRA in a double-hybrid screen performed in yeast and in in vitro protein interaction experiments. HIRIP5 has highly conserved homologs in both prokaryotes and eukaryotes, including the NFU1 gene product which has been implicated in iron metabolism in mitochondria of the yeast Saccharomyces cerevisiae. By radioactive in situ hybridization, the HIRIP5 gene was mapped to the 2p13-p15 chromosomal region, separate from any region previously associated with DiGeorge syndrome.