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At least 811 records · Page 45Linked to original sources
PubMed1987

Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily, regulation, chromosomal mapping, and molecular analysis of the DA rat polymorphism.

Debrisoquine 4-hydroxylase (P450db1) was purified from rat liver microsomes. Polyclonal antibody was produced and, in conjunction with immunoblots, was used to identify and purify a second immunorelated P450 (P450db2) that does not have debrisoquine hydroxylating activity. The cDNA clones to db1 and db2 were isolated from a lambda gt11 expression library, sequenced, and found to share 78% nucleotide and 73% deduced amino acid similarities. These similarities are evenly dispersed along the sequence except for a region of 190 nucleotides with 99% similarity near the carboxyl terminus of the protein-coding region; this similarity is probably the remnant of a gene conversion event. Both proteins share between 38% and 43% amino acid similarity with P450a, P450b, P450e, P450f, P450PB1, and P450j; these data indicate that P450db1 and P450db2 are members of a separate subfamily within the P450II gene family. Southern blot analysis and preliminary genomic cloning suggest that at least four genes exist in the subfamily, although the present evidence suggests that only db1 and db2 are expressed in rat liver. With the use of 19 mouse X hamster somatic cell hybrids, the db1 and db2 genes were localized to mouse chromosome 15 (P450-2D locus). A polymorphism has been described for debrisoquine metabolism in the DA rat strain, adult females having markedly decreased debrisoquine 4-hydroxylase activity. Our immunoblot analysis and mRNA analysis suggest that debrisoquine 4-hydroxylase deficiency in the female DA rat is not due to a decrease in db1 protein or mRNA. The db1 and db2 proteins are differentially regulated: during development db2 is present at birth while db1 is absent, and db1 increases by 1 week of age; in addition, db1 is slightly induced by phenobarbital, 3-methyl-cholanthrene, and dexamethasone whereas db2 is marginally increased by these latter two agents. These results demonstrate that debrisoquine 4-hydroxylase is a member of a new constitutively expressed P450II sub-family containing two or more genes in the rat and establish that the debrisoquine polymorphism in the DA rat is probably due to a structurally altered db1 protein.

Amino Acid Sequence↗
PubMed1991

Genomic organization and chromosomal mapping of the mouse P-cadherin gene.

Cadherins are a family of Ca(2+)-dependent cell adhesion molecules, that includes P-cadherin, E-cadherin, N-cadherin and L-CAM. In this study, the genomic organization of the mouse P-cadherin gene was determined by analyzing overlapping DNA clones obtained from a mouse genomic library. The results showed that this gene spans over 45 kb and consists of 15 exons. A marked feature of this gene is that the first intron is 23 kbp long accounting for half its length. Comparisons of this structure with that of L-CAM, a chicken cadherin, revealed that the exon-intron boundaries are conserved between the two genes except that the P-cadherin first exon includes the correspoding first and second exons of the L-CAM gene. This gene was also similar to the other in that the second intron, which corresponds to the P-cadherin first intron, is exceptionally longer than other introns. These results suggest that the exon-intron pattern conserved in these genes is of significance for generation of domain structure of cadherin molecules or for their transcriptional regulation. We also determined the chromosomal localization of the P-cadherin gene by interspecific backcross analysis, and found that this gene is located in the central region of mouse chromosome 8 and linked with the E-cadherin locus. This is the first evidence for the linkage of different cadherin genes.

Amino Acid Sequence↗
PubMed1994

The murine interleukin-5 receptor alpha-subunit gene: characterization of the gene structure and chromosome mapping.

To understand better the regulation of interleukin-5 receptor alpha-subunit (IL-5R alpha) expression, we have isolated the genomic clones of mouse IL-5R alpha (mIL-5R alpha) and analyzed the structure of the gene. The gene spans more than 35 kb and is composed of 11 exons. We found that two mRNAs encoding secreted forms of mIL-5R alpha result from differential splicing events. We identified the transcriptional start site by primer extension analysis of mIL-5R alpha mRNA. Nucleotide sequence of the 5'-flanking region contains potential binding sites for transcription factor Ap1, AP-1, GATA-1, and PU.1. About 260 bp sequence of the 5'-flanking region exhibited promoter activity when it was linked to a promoterless bacterial chloramphenicol acetyltransferase (CAT) gene. The promoter activity was seen not only in the IL-5-dependent pre-B-cell line Y16, but also in fibroblast cell line NIH-3T3. Comparison of the exon-intron boundaries of mIL-5R alpha genes with those of other members of the cytokine receptor family reveals a conserved evolutionary structure. By fluorescence in situ hybridization analysis, the mIL-5R alpha gene has been assigned to chromosome 6.

Animals↗
PubMed2005

Cloning, structural organization and chromosomal mapping of rat costimulatory molecule 4-1BBL.

4-1BBL (TNFSF9) is a member of the tumor necrosis factor (TNF) ligand superfamily, which is expressed on some activated antigen presenting cells and B cells. We isolated a rat cDNA clone encoding the rat homologue of the human 4-1BBL (GenBank accession No. AY259541). The deduced rat 4-1BBL protein, consisting of 308 amino acids with a molecular weight of 33,469 Da, was a typical type II transmembrane glycoprotein, the same as human and murine 4-1BBL. "SDAA" in the cytoplasmic domain of rat 4-1BBL was deduced to act as the phosphorylation site for casein kinase I ("SXXS" motif), which is present in the cytoplasmic domains of human and murine 4-1BBL, and all other TNF ligand family members known to utilize reverse signaling. The two introns of 4-1BBL were also cloned (GenBank accession No. AY332409). Rat 4-1BBL is much more homologous with murine 4-1BBL than with human 4-1BBL, in both nucleotide and amino acid sequences. Rat 4-1BBL was expressed in all tested tissues: brain, lung, colon, liver, thymus, testicle, kidney, adrenal, stomach, spleen and heart. The chromosomal location of rat 4-1BBL was first identified by bioinformatics, then by fluorescence in situ hybridization at 9q11 (GenBank accession UniGene No. Rn.46783). Rat, murine and human 4-1BBL genes are evolved from a common gene. The identification and characterization of the rat counterpart of human 4-1BBL will facilitate studies of the biological function of this molecule.

4-1BB Ligand↗
PubMed1996

Molecular cloning, chromosomal mapping, and expression of the mouse p107 gene.

Progression through the G1 phase of the cell cycle is regulated, in part, by the pRB-family proteins, pRB and p107. The basis for this regulation is due to a network of interactions between the pRB-family proteins, pRB, p107, and p130; the E2F-family of transcription factors; and cyclins D, E, and A. One of the pRB-family proteins, p107, has also been found to bind to the transactivation domain of the c-Myc proto-oncogene. This region in c-Myc is frequently mutated in tumors such as Burkitt's lymphoma, HIV-associated lymphoma, and multiple myeloma. The binding of p107 and regulation of c-Myc may conceivably be disrupted not only by mutations in c-Myc, but possibly by mutations in p107. In order to determine if mutations in p107 are indeed present in mouse B-cell tumors which exhibit a lower frequency of c-Myc mutation, we have cloned the mouse p107 cDNA and compared this sequence with its human counterpart. We find that the extreme N-terminal and C-terminal regions are the most conserved between human and mouse p107 sequences. Chromosomal positioning of the locus for p107 (designated Rbl1) as well as E2f1 to the distal end of mouse Chromosome (Chr) 2 also suggests a close but unlinked genetic relationship between these cell cycle regulatory transcription factors.

Animals↗
PubMed1998

Cloning and chromosomal mapping of the murine norepinephrine transporter.

The norepinephrine (NE) transporter (NET), a target of many clinically prescribed antidepressants, regulates noradrenergic neurotransmission by efficiently clearing NE from synaptic spaces after release. To advance our understanding of NET gene structure, regulation, and potential associations with complex behavioral trait loci, we amplified a mouse norepinephrine transporter (mNET) cDNA from placenta total RNA and utilized mNET probes to isolate and characterize the mNET gene. Inferred translation of the major open reading frame of the mNET cDNA predicts a 617-amino acid protein with 12 putative membrane-spanning regions and 94% identity to human NET. The coding exons of the mNET cDNA were found to be spread across >36 kb of 129/Svj genomic DNA, with exon-intron boundaries bearing consensus gt/ag splice sites. Sequence upstream (202 bp) of the inferred translation initiation site matched the sequence of 5' rapid amplification of cDNA ends products from brain mRNA with no evidence for intervening introns and is preceded by a TATA box and canonical transcriptional regulatory elements that may play a role in mNET expression in vivo. Probes derived from mNET cDNA identified species-specific MspI restriction fragment length variations within the mNET gene that were utilized to position the gene (Slc6a5) to murine chromosome 8, one recombinant distal to D8Mit15. This site is within a recently defined quantitative trait locus defined for ethanol sensitivity in LSXSS recombinant inbred mice, Lore4. The status of Slc6a5 as a candidate gene for alcohol sensitivity is discussed with respect to studies noting ethanol-induced alterations in brain NE receptors, NE receptor-linked adenylate cyclase, and NE transport.

Amino Acid Sequence↗
PubMed2001

Physical state of HPV16 and chromosomal mapping of the integrated form in cervical carcinomas.

Using a procedure based on restriction enzyme cleavage, self-ligation, and inverse polymerase chain reaction (rliPCR), the authors investigated 18 cervical intraepithelial neoplasia III (CIN III) cases and 37 invasive squamous carcinomas for integration of human papillomavirus type 16 (HPV16). All eighteen CIN III cases (severe dysplasia or high-grade squamous intraepithelial lesion) were found to harbor episomal HPV, but one of the samples contained mixed episomal and integrated forms. Seventeen of 37 invasive cervical carcinoma samples were identified previously as containing the completely integrated HPV16 genome by using PCR covering the entire E1/E2 gene, and this was confirmed by rliPCR in 16 cases. One case, however, showed a low level of episomal deoxyribonucleic acid in addition to the predominant integrated form. Of the remaining 20 carcinoma samples showing episomal forms in the previous analysis, 14 were found to contain integrated forms using rliPCR, and four contained multimeric episomal forms. Thus, in total, 31 of 37 of the carcinomas (84%) showed the integrated HPV16 genome. The rliPCR product from five carcinoma cases was cloned into a plasmid vector and used as a template for "primer walking" deoxyribonucleic acid sequencing to deduce human sequences flanking the integrated HPV genome. Based on this information, bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) clones were obtained and used as probes in fluorescent in situ hybridization experiments on human metaphase chromosomes. The results of the fluorescent in situ hybridization experiments showed evidence for HPV16 integration in chromosome regions 1q25, 3q28, 6p25, 11p13, and 18q22. Sixteen carcinoma samples, containing episomal HPV16, were sequenced in the long control region. Evidence for changes in E2 binding or silencer YY1 sequences was found in only two samples.

Blotting, Southern↗
PubMed2002

Molecular characterisation and chromosomal mapping of transcripts having tissue-specific expression in the malaria mosquito Anopheles gambiae: possible involvement in visual or olfactory processes.

We have compared the transcriptional activity of heads, antennae + palps, and carcasses in the mosquito Anopheles gambiae by means of differential display PCR (DD-PCR). Three transcripts specifically or preferentially expressed in the heads and in the antennae + palps have been selected. All are very similar to genes related to visual and olfactory mechanisms of several different organisms. They have been named Ag arrestin, Ag rLDL, and Ag dynamin. The potential of the DD-PCR technique in identifying genes involved in mosquito behaviour and the usefulness of the molecular characterisation of these transcripts are discussed.

Amino Acid Sequence↗
PubMed1993

Cell binding specificity of mouse R-cadherin and chromosomal mapping of the gene.

R-cadherin was originally identified as a chicken cadherin expressed by the retina. Here, we describe the identification of a mouse homologue of R-cadherin. We isolated mouse cDNAs encoding a cadherin with 94% identity in amino acid sequence to the chicken R-cadherin, and defined this molecule as mouse R-cadherin. L cells transfected with the mouse R-cadherin cDNA acquired a cadherin-mediated cell-cell adhesiveness as found for other cadherins. To examine the binding specificity of mouse R-cadherin, L cells expressing this cadherin (mRL) were mixed with L cells expressing chicken R-cadherin (cRL), mouse N-cadherin (mNL), mouse E-cadherin (mEL) and mouse P-cadherin (mPL). While mRL cells randomly intermixed with cRL cells, those cells aggregated separately from mEL or mPL cells. Mixing of mRL with mNL cells gave an intermediate result; that is, they formed both separate and chimeric aggregates, suggesting that R- and N-cadherin can interact with each other although each has a preference to bind to its own type. Similar properties were previously found for chicken R-cadherin. Thus, the cell binding specificity of R-cadherin is entirely conserved between the two species, suggesting a conserved role for this protein in morphogenesis. We also located the mouse R-cadherin gene to chromosome 2.

Amino Acid Sequence↗
PubMed1992

Genomic structure and chromosomal mapping of the mouse N-cadherin gene.

N-cadherin is a member of the cadherin cell-cell adhesion receptor family that includes P-, E-, and R-cadherin and liver cell adhesion molecule (L-CAM). In this study, we determined the structure of the mouse N-cadherin gene by analyzing overlapping genomic clones obtained from a mouse genomic library. This gene consists of 16 exons that disperse over greater than 200 kilobases of genomic DNA. This large size of the N-cadherin gene, compared with its cDNA (4.3 kilobases), is ascribed to the fact that the first and second introns are 34.2 kilobases and greater than 100 kilobases long, respectively. When the N-cadherin gene was compared with that of L-CAM and P-cadherin, the exon-intron boundaries were found to be fully conserved between them, except that the P-cadherin first exon includes the first and second exons of the other two genes. Also, the second intron, which is equivalent to the first intron in P-cadherin, is exceptionally large and this structural feature is conserved in all of these genes. An interesting feature of the N-cadherin gene is that this gene has an extra 16th exon that is almost identical to the other exon, 100% in the coding region and 99% in the 3' untranslated region in the nucleotide level. We also determined the chromosomal localization of the N-cadherin gene by interspecific backcross analysis and found that this gene is localized in the proximal region of mouse chromosome 18. The E- and P-cadherin genes are tightly linked and located on chromosome 8 in this species. Thus, N-cadherin is unlinked to these other cadherin loci.

Amino Acid Sequence↗
PubMed2000

Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic seizures.

PURPOSE: NER is a mutant rat strain that exhibits spontaneous tonic-clonic convulsions accompanied by epileptic discharges on ictal EEG and serves as a model for generalized tonic-clonic seizures in humans. Our previous experiments have suggested that a major autosomal recessive gene and several minor genes regulate the inheritance of tonic-clonic seizures in NER. The purpose of this study was to confirm the mode of inheritance and to locate the causative genes for epilepsy in NER on the rat genetic map. METHODS: We developed F1 hybrid (F1) and reciprocal back-cross progenies of NER with a seizure-resistant strain, F344, and evaluated their seizure susceptibility under tossing-stimulated and nonstimulated conditions. Backcross animals were genotyped using simple sequence length polymorphism markers for polymerase chain reactions. Linkage between seizure susceptibility and marker loci was analyzed by chi2 statistic tests and by the computer programs MAPMAKER/EXP and MAPMAKER/QTL. RESULTS: Under tossing-stimulating conditions, tonic-clonic seizures were provoked in 90% of NER and 66% of (F1 x NER) backcross animals, but no seizures occurred in the F344, F1, or (F1 x F344) backcross animals. Routine monitoring of nonstimulated animals revealed spontaneous tonic-clonic convulsions in 100% of NER and 64.2% of (F1 x NER) backcross animals, but no seizures in F344 or F1. Gender effect on seizure susceptibility was negligible in (F1 x NER) backcross in both conditions. Preliminary genome-wide scanning and subsequent precise location of the causative genes revealed seizure susceptibility loci, designated Ner1 and Ner2, on rat chromosomes 1 and 3, respectively. CONCLUSIONS: Ner1 is a locus that controls the inheritance of spontaneous tonic-clonic seizures in an autosomal recessive mode, whereas Ner2 affects the occurrence of tossing-induced seizures. Orthologous genes in the vicinity of these loci may be related to epileptogenesis in other species, including humans.

Animals↗
PubMed1996

Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease.

Stroke is a complex disorder with a poorly understood multifactorial and polygenic aetiology. We used the stroke-prone spontaneously hypertensive rat (SHRSP) as a model organism, mated it with the stroke-resistant spontaneously hypertensive rat (SHR) and performed a genome-wide screen in the resultant F2 cohort where latency until stroke, but not hypertension (a major confounder) segregated. We identified three major quantitative trait loci, STR1-3, with lod scores of 7.4, 4.7 and 3.0, respectively, that account for 28% of the overall phenotypic variance. STR2 colocalizes with the genes encoding atrial and brain natriuretic factor, peptides with important vasoactive properties. Our results demonstrate the existence of primary, blood pressure-independent genetic factors predisposing to a complex form of stroke.

Animals↗
PubMed1990

cDNA sequence, tissue-specific expression, and chromosomal mapping of the human slow-twitch skeletal muscle isoform of troponin I.

Troponin I (TnI) is a myofibrillar protein involved in the calcium-mediated regulation of striated muscle contraction. Three isoforms of TnI are known and each is expressed in a muscle fiber-type-specific manner. TnI-fast and TnI-slow are expressed exclusively in fast-twitch and slow-twitch skeletal muscle myofibers, respectively, while a third isoform, TnI-card, is expressed in both the atrium and the ventricle of the heart. An explanation of the myofiber-type-restricted expression of the troponin I multigene family will further aid in understanding how various types of striated muscle fibers are established. To initiate the study of TnI isoform gene expression, we have isolated a full-length cDNA representing the human slow-twitch skeletal muscle isoform of troponin I. Sequence comparisons demonstrate that the TnI-slow protein is highly conserved between species. Therefore, the cDNA was used as a probe to investigate the tissue-specific and developmental regulation of the TnI-slow gene in both rodent and human myogenic cells. TnI-slow message appears to be restricted to muscle tissue containing slow-twitch skeletal muscle myofibers. TnI-slow gene expression is induced in differentiated cultures of primary human muscle cells and several (but not all) myogenic cell lines. In addition, a human-specific probe prepared from the 3' untranslated region of the cDNA has been used to probe a panel of human/mouse somatic cell hybrid lines, resulting in the assignment of the human TnI-slow gene to the q12----qter region of chromosome 1. The locus is designated TNNI1.

Amino Acid Sequence↗
PubMed2003

Cloning of laminin gamma2 cDNA and chromosome mapping of the genes for the dog adhesion ligand laminin 5.

Overexpression of the gamma2 chain of laminin-5 has been linked to tumor invasion and an unfavorable prognostic value, but the role of this adhesion molecule in cancer progression remains unclear. Because dog models of human cancers provide the opportunity of clarifying the relation between laminin-5 and tumor malignancy we have isolated and characterized the cDNA of dog gamma2 chain. Comparative analysis of the nucleotide sequence revealed high identity between the dog and the human gamma2, including the intermolecular molecule binding sites and the regulatory promoter sequences. Moreover, expression of a recombinant human gamma2 chain in dog keratinocytes results in assembly and secretion of hybrid laminin-5 molecules, which underscore the functional relevance of the gamma2 conserved domains. We have also determined the syntenic location of the dog laminin-5 loci on CFA7. Our study provides a basis for therapeutical approaches of epithelial cancers of gamma2 using dogs as large animal models.

Amino Acid Sequence↗
PubMed1998

Promoter sequence, expression, and fine chromosomal mapping of the human gene (MLP) encoding the MARCKS-like protein: identification of neighboring and linked polymorphic loci for MLP and MACS and use in the evaluation of human neural tube defects.

The MARCKS-like protein (MLP), also known as F52, MacMARCKS, or MARCKS-related protein, is a widely distributed substrate for protein kinase C (PKC). Recent studies using gene disruption in vivo have demonstrated the importance of both MARCKS and MLP to the development of the central nervous system; specifically, mice lacking either protein exhibit a high frequency of neural tube defects. We isolated a genomic clone for human MLP and discovered a directly linked polymorphism (MLP1) useful for genetic linkage analysis. The MLP promoter was 71% identical over 433 bp to that of the corresponding mouse gene, Mlp, with conservation of many putative transcription factor-binding sites; it was only 36% identical over 433 bp to the promoter of the human gene, MACS, which encodes the MLP homologue MARCKS. This 433-bp fragment drove expression of an MLP-beta-galactosidase transgene in a tissue-specific and developmental expression pattern that was similar to that observed for the endogenous gene, as shown by in situ hybridization histochemistry. In contrast to MACS, the MLP and Mlp promoters contain a TATA box approximately 40 bp 5' of the presumed transcription initiation site. MLP was localized to chromosome 1p34-->1pter by analysis of human-mouse somatic cell hybrid DNA and to 1p34 by fluorescence in situ hybridization. Radiation hybrid mapping of MLP placed it between genetic markers D1S511 (LOD > 3.0) and WI9232. MACS was localized to 6q21 between D6S266 (LOD > 3.0) and AFM268uh5 by the same technique. We tested the novel MLP1 polymorphism and the MACS flanking markers in a series of 43 Caucasian simplex families in which the affected child had a lumbosacral myelomeningocele. We found no evidence of linkage disequilibrium, suggesting that these loci were not major genes for spina bifida in these families. Nonetheless, the identification of linked and neighboring polymorphisms for MACS and MLP should permit similar genetic studies in other groups of patients with neural tube defects and other neurodevelopmental abnormalities.

Animals↗
PubMed2000

Genomic cloning, chromosomal mapping, and expression analysis of msal-2.

Mutations of SALL1 related to spalt of Drosophila have been found to cause Townes-Brocks syndrome, suggesting a function of SALL1 for the development of anus, limbs, ears, and kidneys. No function is yet known for SALL2, another human spalt-like gene. The structure of SALL2 is different from SALL1 and all other vertebrate spalt-like genes described in mouse, Xenopus, and Medaka, suggesting that SALL2-like genes might also exist in other vertebrates. Consistent with this hypothesis, we isolated and characterized a SALL2 homologous mouse gene, Msal-2. In contrast to other vertebrate spalt-like genes both SALL2 and Msal-2 encode only three double zinc finger domains, the most carboxyterminal of which only distantly resembles spalt-like zinc fingers. The evolutionary conservation of SALL2/Msal-2 suggests that two lines of sal-like genes with presumably different functions arose from an early evolutionary duplication of a common ancestor gene. Msal-2 is expressed throughout embryonic development but also in adult tissues, predominantly in brain. However, the function of SALL2/Msal-2 still needs to be determined.

Amino Acid Sequence↗
PubMed2005

TileMap: create chromosomal map of tiling array hybridizations.

MOTIVATION: Tiling array is a new type of microarray that can be used to survey genomic transcriptional activities and transcription factor binding sites at high resolution. The goal of this paper is to develop effective statistical tools to identify genomic loci that show transcriptional or protein binding patterns of interest. RESULTS: A two-step approach is proposed and is implemented in TileMap. In the first step, a test-statistic is computed for each probe based on a hierarchical empirical Bayes model. In the second step, the test-statistics of probes within a genomic region are used to infer whether the region is of interest or not. Hierarchical empirical Bayes model shrinks variance estimates and increases sensitivity of the analysis. It allows complex multiple sample comparisons that are essential for the study of temporal and spatial patterns of hybridization across different experimental conditions. Neighboring probes are combined through a moving average method (MA) or a hidden Markov model (HMM). Unbalanced mixture subtraction is proposed to provide approximate estimates of false discovery rate for MA and model parameters for HMM. AVAILABILITY: TileMap is freely available at http://biogibbs.stanford.edu/~jihk/TileMap/index.htm. SUPPLEMENTARY INFORMATION: http://biogibbs.stanford.edu/~jihk/TileMap/index.htm (includes coloured versions of all figures).

Algorithms↗
PubMed2001

Identification, genomic organization, chromosomal mapping and mutation analysis of the human INV gene, the ortholog of a murine gene implicated in left-right axis development and biliary atresia.

Determination of left-right axis is a precocious embryonic event, and all phenotypic anomalies resulting from disruption of the normal lateralization process are collectively referred to as the lateralization defect. A transgenic mouse with lateralization defect and hepatic, kidney, and pancreatic anomalies has resulted from disruption of the inv gene by insertion of a transgene. The human ortholog is thus a good candidate for lateralization defect in humans, in particular in cases with associated hepatic anomalies. Here, we have identified, mapped, and characterized the INV human gene and screened a series of heterotaxic patients (with or without biliary anomalies) for mutation in this gene. In a German family of Turkish origin, we have found that all available affected and unaffected individuals are heterozygous for a mutation in the splicing donor site of intron 12 in the INV gene resulting in two different aberrant splicing isoforms. This can be explained either by a randomization of lateralization defects or, as suggested earlier, di- or trigenic inheritance, although we have been unable to detect, in this family, a mutation in genes known to be involved in the human lateralization defect ( LEFTY1, LEFTY2, ACVR2B, NODAL, ZIC3, and CFC1). In contrast to the mouse, the affected individuals have no biliary anomalies, and the absence of mutation in a series of seven cases with lateralization defect and biliary anomalies demonstrates that INV is not frequently involved in such a phenotype in humans.

Amino Acid Sequence↗