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PubMed2001

A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family.

PURPOSE: To describe a novel gene causing a Stargardt-like phenotype in a family with dominant macular dystrophy and the exclusion of all known genes within the disease locus. METHODS: Meiotic breakpoint mapping in a family of 2314 individuals enabled refinement of the location of the disease gene. The genomic organization and expression profile of known and putative genes within the critical region were determined using bioinformatics, cDNA cloning, and RT-PCR. The coding sequence of genes expressed within the retina was scanned for mutations, by using DNA sequencing. RESULTS: The disease-causing gene (STGD3) was further localized to 562 kb on chromosome 6 between D6S460 and a new polymorphic marker centromeric to D6S1707. Of the four genes identified within this region, all were expressed in the retina or retinal pigment epithelium. The only coding DNA sequence variant identified in these four genes was a 5-bp deletion in exon 6 of ELOVL4. The deletion is predicted to lead to a truncated protein with a net loss of 44 amino acids, including a dilysine endoplasmic reticulum retention motif. The ELOVL4 gene is the fourth known example of a predicted human protein with homology to mammalian and yeast enzymes involved in the membrane-bound fatty acid chain elongation system. The genomic organization of ELOVL4 and primer sets for exon amplification are presented. CONCLUSIONS: ELOVL4 causes macular dystrophy in this large family distributed throughout North America and implicates fatty acid biosynthesis in the pathogenesis of macular degeneration. The PCR-based assay for the 5-bp deletion will facilitate more accurate genetic counseling and identification of other branches of the family.

Amino Acid Sequence↗
PubMed1990

Prevalence and polymorphism of human VH3 genes.

To better understand heterogeneity of human VH genes, we have studied polymorphism among three homologous genes from VH3, the most complex human VH gene family. Sequence-specific oligonucleotide probes were used to identify the germ-line source of each gene. The fetally expressed gene 56p1, and the germ-line VH element 1.9III, were identified and shown to be distinct. Also identified was T5M10, a VH element that resembles 56p1 and 1.9III, and likely corresponds to the previously described germ-line gene, hv3005. The elements 56p1, 1.9III, and T5M10 were each polymorphic, and in 52 unrelated individuals, their prevalences were 62%, 92%, and 35%, respectively. Among individuals lacking the hybridization bands characteristic of 56p1, 1.9III, or T5M10, alternative RFLP or coding region sequence variants were not found. In the population studied, these three VH elements were present in five different combinations, and at least three haplotypes. The distribution of these VH elements indicated they are not alleles of a single locus, and 56p1 and 1.9III are probably not alleles of each other. These results suggest that polymorphism is commonplace among human VH3 genes, but that a limited number of conserved alleles dominate each locus. We conclude that heterogeneity in the VH germ-line repertoire may derive more from diversity of haplotypes than from diversity of alleles.

Alleles↗
PubMed1988

Genetic defect responsible for the dysfunctional protein: factor IXLong Beach.

DNA sequence analysis of the gene coding for the variant protein, factor IXLong Beach (FIXLB), has identified a transition mutation in an otherwise normal factor IX (FIX) gene. Genomic DNA clones spanning 35 kilobase (kb) pairs of the FIXLB gene were isolated. A gene analysis strategy that specifically characterized exons and their flanking intron sequences predicted the entire amino acid sequence of FIXLB. A thymine to cytosine transition causes the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon VIII of the FIXLB gene. This mutation results in an amino acid substitution at residue 397 of the FIX zymogen and the phenotypic display of hemophilia-B. Previous studies revealed that activated purified FIXLB (FIXaLB) had normal Ca2+, phospholipid, and factor VIIIa binding characteristics. However, FIXaLB activated factor X or factor VII (with their cofactors Ca2+ and phospholipid) at significantly reduced rates, suggesting that the defect in FIXaLB lies near or within the catalytic triad of the FIX heavy chain. Identification of an amino acid substitution near the carboxy-terminus of the FIXaLB heavy chain supports the earlier characterization of this variant protein. Moreover, our data identify a residue in the catalytic domain of FIXa essential for normal function.

Base Sequence↗
PubMed1993

FVT-1, a novel human transcription unit affected by variant translocation t(2;18)(p11;q21) of follicular lymphoma.

Variant t(2;18) and t(18;22) chromosome translocations observed in B-cell chronic lymphocytic leukemias and in follicular lymphomas have been reported to consistently involve the 5' region of the BCL-2 gene on chromosome 18 and various regions on the lg light chain loci. We show here that a variant t(2;18)(p11;q21) translocation observed in a case of follicular lymphoma leads to the juxtaposition of a J kappa segment to a chromosome 18 transcriptional unit located 10 kpb upstream of the BCL-2 locus. The cDNA of this new evolutionarily conserved gene, termed FVT-1 for follicular-variant-translocation gene, codes for a putatively secreted protein of 36 Kd that is not homologous with any described protein. The FVT-1 gene is weakly expressed in all the analyzed normal hematopoietic tissues but a very high rate of transcription is observed in some T-cell malignancies and in phytohemagglutinin-stimulated lymphocytes. The proximity of FVT-1 to the BCL-2 locus suggests that in the t(14;18) currently observed in follicular lymphomas, both genes would participate in the tumoral process.

Amino Acid Sequence↗
PubMed1996

Linkage, association and mutational analysis of the dopamine D3 receptor gene in schizophrenia.

This study follows the observation of an association between homozygosity of an Mscl polymorphism in exon 1 and schizophrenia, which gives rise to a glycine to serine substitution and may alter the functional properties of the receptor. Alternatively the polymorphism may not itself be of functional significance but may be in linkage disequilibrium with another genetic variant in the coding or regulatory regions. To examine the second possibility we have screened all six exons of DRD3 by single-stranded conformational polymorphism analysis (SSCP) in 36 cases and 36 controls. Our findings suggest that the gene is highly conserved since we found no other mutations which alter protein structure. However we did detect a 5-bp deletion in the 3' intronic sequence flanking exon 5 which occurred in 7-8% of subjects within both case and control samples. A single bp substitution (g to a) in exon 3, which does not alter an amino acid was found in one affected individual. In addition we carried out a linkage study of 24 families multiply affected with schizophrenia and a non-parametric linkage study of 90 affected sibling pairs. These studies give no support for either major or moderate gene effects on schizophrenia susceptibility. Finally we have extended our association sample and observe a non-significant excess of homozygotes for the Mscl polymorphism in the sample overall (chi 2 = 2.09, 1 d.f., P = 0.15). The excess of homozygotes is specific to males (chi 2 = 4.617, 1 d.f., P = 0.032) and not females (chi 2 = 0.243, 1 d.f., NS). When these data are added to our previous published data a highly significant excess of homozygotes is observed in males (chi 2 = 13.766, 1 d.f., P = 0.00021) but not females (chi 2 = 0.606, 1 d.f., NS). In conclusion the accumulated data suggest strongly that genetic variation at the DRD3 locus increases susceptibility of schizophrenia, at least in males. At present the Mscl polymorphism in exon 1 of the gene remains a candidate for bringing about functional change in the receptor but this has not been formally tested. Other coding region polymorphisms have not been detected but it remains possible that variation within the promoter may alter receptor function.

Base Sequence↗
PubMed1997

Discrimination of hepatitis G virus/GBV-C geographical variants by analysis of the 5' non-coding region.

We have investigated the ability of different subgenomic fragments to reproduce the phylogenetic relationships observed between six complete genome sequences of GBV-C/hepatitis G virus (HGV). While similar relationships were observed following analysis of part of the 5' non-coding region (5'NCR), for the coding region they were not accurately reproduced for some large fragments or for the majority of fragments of 300 or 600 nucleotides. Analysis of 5'NCR sequences from a large number of isolates, including newly obtained sequences from Pakistan, Zaïre and Scotland, produced separate groupings of Asian, African and European/North American variants. These groupings are associated with specific polymorphisms in the 5'NCR, many of which were covariant and consistent with a proposed secondary structure for this region. The relatively low level of amino acid sequence variation observed between these geographically and phylogenetically defined groups of variants suggests that they are unlikely to display significant biological differences.

Base Sequence↗
PubMed1986

Sequences of four mouse histone H3 genes: implications for evolution of mouse histone genes.

The sequences of four histone H3 genes coding for the replication variant proteins H3.1 and H3.2 have been determined. Three of these genes, two coding for H3.1 proteins and one for an H3.2 protein, are located on chromosome 13 and expressed at low levels. The fourth gene, encoding an H3.2 protein, is located on chromosome 3 and expressed at a high level. The coding regions of the three genes on chromosome 13 are more similar to each other than to the H3 gene on chromosome 3, and equally divergent from it, suggesting that either gene duplication or gene conversion has occurred since the genes were dispersed onto two chromosomes. A 14-base sequence including the CCAAT sequence and located 5' to the genes on chromosome 13 has been conserved. The histone H3 gene on chromosome 3 has multiple potential binding sites for the Sp1 transcription factor. The coding regions show greater than 95% conservation among the four genes. This is due to the strict pattern of codon usage and the presence of two long (greater than 60 base) regions of completely conserved nucleic acid sequence. These conserved regions in the coding sequence may have an important functional role at the mRNA or DNA level.

Amino Acid Sequence↗
PubMed1988

Growth hormones. 1. Polymorphism (minireview).

Pituitary growth hormone (GH) is not a single molecular species, but a whole set of similar molecules, the individual specific characteristics of which constitute the polymorphism of this hormone. The present paper deals mainly with various forms of human GH, called "variants", and touches on this polymorphism in other species as well. The 22 K variant (MW = 22,000 daltons) is the predominant form of GH to which all other variants are compared as to chemical structure and biological effect. These variants are classified into two large groups: 1) mass variants, the molecular weight of which is modified in comparison with that of 22 K; these can be subdivided into aggregated and non-aggregated forms, and 2) charge variants with modified electrophoretic mobility. Outside this classification are entities which are not yet well known; these include bioinactive GH, correctly detected by RIA but deprived of biological activity or, on the contrary, strongly bioactive GH lacking immunoreactivity and consequently difficult to study. Another outsider is the SV-hGH-2 variant encoded from a gene different from the hGH-N gene normally coding for the other variants. In this case, the product could be considered a true isohormone of 22 K and no longer a variant. The pituitary expression of this gene has never been evidenced to date, but according to recent data, it could be expressed at the placental level and be implicated in human placental growth hormone (hPGH) synthesis. hPGH is a newly-found GH in pregnant women which takes over pituitary GH from the 25th week onwards. After the GH molecules are released by the pituitary in the blood stream, they are partially taken up and carried by binding proteins. The physiological role of this phenomenon could be the setting up of a GH reservoir and a GH sparing process since the metabolic clearance rate of the complex GH-binding protein is slower than that of free GH, thus increasing the biological half-life of the hormone.

Animals↗
PubMed1997

Human cholecystokinin type A receptor gene: cytogenetic localization, physical mapping, and identification of two missense variants in patients with obesity and non-insulin-dependent diabetes mellitus (NIDDM).

The human CCKAR gene was previously mapped to chromosome 4 using a panel of human/hamster somatic cell hybrids. We now report the cytogenetic and physical localization of the CCKAR gene. Using fluorescence in situ hybridization, we determined that CCKAR maps to 4p15.1-p15.2. On the physical map, CCKAR was adjacent to the marker AFMa283yh5, between AFMb355ya5 and WI-4086. A simple sequence repeat (D4S391) with high heterozygosity was found in the database, and CCKAR and this genetic marker were colocalized on two YACs (933D9 and 928A5). We also characterized the genomic structure and determined the exon-intron boundaries of the gene. This provided the opportunity to screen the gene in patients with non-insulin-dependent diabetes mellitus and/or obesity for single nucleotide changes using a single-strand conformational polymorphism strategy. Five sequence variants were identified in the coding sequence of the gene, including two missense variants (G21R and V365I). The results of these studies provide (1) precise genetic and physical mapping data, (2) exon-intron sequences for single nucleotide analysis, and (3) identification of two missense mutations in the CCKAR gene. The contribution of these CCKAR variants to normal physiology, to obesity, and to diabetes can now be evaluated.

Animals↗
PubMed2005

The role of alternative translation start sites in the generation of human protein diversity.

According to the scanning model, 40S ribosomal subunits initiate translation at the first (5' proximal) AUG codon they encounter. However, if the first AUG is in a suboptimal context, it may not be recognized, and translation can then initiate at downstream AUG(s). In this way, a single RNA can produce several variant products. Earlier experiments suggested that some of these additional protein variants might be functionally important. We have analysed human mRNAs that have AUG triplets in 5' untranslated regions and mRNAs in which the annotated translational start codon is located in a suboptimal context. It was found that 3% of human mRNAs have the potential to encode N-terminally extended variants of the annotated proteins and 12% could code for N-truncated variants. The predicted subcellular localizations of these protein variants were compared: 31% of the N-extended proteins and 30% of the N-truncated proteins were predicted to localize to subcellular compartments that differed from those targeted by the annotated protein forms. These results suggest that additional AUGs may frequently be exploited for the synthesis of proteins that possess novel functional properties.

5' Untranslated Regions↗
PubMed2001

Retinoic acid receptor alpha1 variants, RARalpha1DeltaB and RARalpha1DeltaBC, define a new class of nuclear receptor isoforms.

Retinoic acid (RA) binds and activates retinoid X receptor (RXR)/retinoic acid receptor (RAR) heterodimers, which regulate the transcription of genes that have retinoic acid response elements (RARE). The RAR isotypes (alpha, beta and gamma) are comprised of six regions designated A-F. Two isoforms of RARalpha, 1 and 2, have been identified in humans, which have different A regions generated by differential promoter usage and alternative splicing. We have isolated two new splice variants of RARalpha1 from human B lymphocytes. In one of these variants, exon 2 is juxtaposed to exon 5, resulting in an altered reading frame and a stop codon. This variant, designated RARalpha1DeltaB, does not code for a functional receptor. In the second variant, exon 2 is juxtaposed to exon 6, maintaining the reading frame. This isoform, designated RARalpha1DeltaBC, retains most of the functional domains of RARalpha1, but omits the transactivation domain AF-1 and the DNA-binding domain. Consequently, it does not bind nor transactivate RARE on its own. Nevertheless, RARalpha1DeltaBC interacts with RXRalpha and, as an RXRalpha/RARalpha1DeltaBC heterodimer, transactivates the DR5 RARE upon all-trans-RA binding. The use of RAR- and RXR-specific ligands shows that, whereas transactivation of the DR5 RARE through the RXRalpha/RARalpha1 heterodimer is mediated only by RAR ligands, transactivation through the RXRalpha/RARalpha1DeltaBC heterodimer is mediated by RAR and RXR ligands. Whilst RARalpha1 has a broad tissue distribution, RARalpha1DeltaBC has a more heterogeneous distribution, but with significant expression in myeloid cells. RARalpha1DeltaBC is an infrequent example of a functional nuclear receptor which deletes the DNA-binding domain.

Alternative Splicing↗
PubMed2000

The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines.

The human T cell transcription factor-4 (hTCF-4) interacts functionally with beta-catenin in the Wnt signaling pathway, which regulates many developmental processes. Moreover, inappropriate reactivation of this pathway attributable to APC or beta-catenin mutations has been described in colorectal cancers. Because only the human TCF-4 cDNA sequence was known, we determined its genomic structure. A total of 17 exons, of which 5 were alternative, were identified. Moreover, four alternative splice sites were observed either experimentally or in silico by a BLAST approach in expressed sequence tag databases. The alternative use of three consecutive exons localized in the 3' part of the hTCF-4 gene changes the reading frames used in the last exon, leading to the synthesis of a number of hTCF-4 isoforms with short, medium, or long-size COOH-terminal ends. We next screened the entire hTCF-4 gene for mutations in a series of 24 colorectal cancer cell lines by denaturing gradient gel electrophoresis and/or direct sequencing. Besides an already described deletion of an A in an (A)9 coding repeat in four cases, we found DNA variants in eight cases for a total of 12 variants, of which 8 were coding. These include one frameshift mutation in the beta-catenin binding domain (exon 1), and one missense mutation in exon 4. In the remaining six cases, nonsense or frameshift mutations were localized in the 3' part of the gene. These latter alterations have as a common consequence to decrease the proportion of the long COOH-terminal hTCF-4 isoform, which contains two binding domains for c-terminal binding protein, a protein implicated in the repression of the TCF family transcriptional activity. Thus, loss of the TCF-4 capacity to interact with COOH-terminal binding protein could be an important event during colorectal carcinogenesis by modifying Wnt signaling.

Alternative Splicing↗
PubMed2003

Amino acid code of protein secondary structure.

The calculation of protein three-dimensional structure from the amino acid sequence is a fundamental problem to be solved. This paper presents principles of the code theory of protein secondary structure, and their consequence--the amino acid code of protein secondary structure. The doublet code model of protein secondary structure, developed earlier by the author (Shestopalov, 1990), is part of this theory. The theory basis are: 1) the name secondary structure is assigned to the conformation, stabilized only by the nearest (intraresidual) and middle-range (at a distance no more than that between residues i and i + 5) interactions; 2) the secondary structure consists of regular (alpha-helical and beta-structural) and irregular (coil) segments; 3) the alpha-helices, beta-strands and coil segments are encoded, respectively, by residue pairs (i, i + 4), (i, i + 2), (i, i = 1), according to the numbers of residues per period, 3.6, 2, 1; 4) all such pairs in the amino acid sequence are codons for elementary structural elements, or structurons; 5) the codons are divided into 21 types depending on their strength, i.e. their encoding capability; 6) overlappings of structurons of one and the same structure generate the longer segments of this structure; 7) overlapping of structurons of different structures is forbidden, and therefore selection of codons is required, the codon selection is hierarchic; 8) the code theory of protein secondary structure generates six variants of the amino acid code of protein secondary structure. There are two possible kinds of model construction based on the theory: the physical one using physical properties of amino acid residues, and the statistical one using results of statistical analysis of a great body of structural data. Some evident consequences of the theory are: a) the theory can be used for calculating the secondary structure from the amino acid sequence as a partial solution of the problem of calculation of protein three-dimensional structure from the amino acid sequence, and the calculated secondary structure and codon strength distribution can be used for simulating the next step of protein folding; b) one can propose that the same secondary structures can be folded into different tertiary structures and, vice versa, different secondary structures can be folded into the same tertiary structures, provided codon distributions are considered also; c) codons can be considered as first elements of protein three-dimensional structure language.

Amino Acid Sequence↗
PubMed2003

Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility.

As the central component of the human endotoxin sensor, Toll-like receptor 4 (TLR4) functions in the early detection and response to Gram-negative infection. We therefore examined a large collection of patients with meningococcal sepsis, comparing the frequency of rare TLR4 coding changes to those in an ethnically matched control population. TLR2 sequences were also acquired and compared. Total nucleotide variation at TLR4 and TLR2 loci was assayed by using a novel computational method. A total of 3.01 megabases of coding sequence was captured at these loci from white subjects with or without meningococcal disease. Authentic mutations were found and high-quality, bidirectional coverage was measured across the coding region by using mutationseeker, a program specifically designed to assay locus-specific genetic load. Using a method that obviates the confounding effect of linkage disequilibrium, we observed that rare heterozygous missense mutations of TLR4 contribute to the development of systemic meningococcal disease among white populations of the southern United Kingdom (P = 0.02; odds ratio 8.2). When results from all white populations were pooled, an overwhelmingly significant excess of such mutations was observed among individuals with disease (P = 2 x 10(-6); odds ratio 27.0). The common white TLR4 variant (TLR4B), synonymous TLR4 substitutions, and variant TLR2 alleles were not significantly over-represented among patients with systemic meningococcal infections. No single variant of TLR4 was significantly over-represented in the meningococcal population. Collectively, however, rare TLR4 coding variants were markedly over-represented. Sensing via TLR4 probably contributes to the early containment of meningococcal infection, and sensing defects create increased risk of disease.

Alleles↗
PubMed2005

The coding sequence of the ASIP gene is identical in nine wild-type coloured cattle breeds.

The aim of this study was to ascertain the role of the Agouti signaling peptide (ASIP) gene coding region in the Agouti locus variation within wild-type coat colour in cattle. We determined the Extension genotype in 241 individuals from six Spanish and three French brown cattle breeds representative of wild-type coat variation. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis was carried out in individuals of each Extension genotypes within the same breed in an attempt to identify variants in the three coding exons of the ASIP gene. No SSCP variants were found. Results were confirmed by sequencing the coding exons of the ASIP gene in 20 individuals. Our results suggest that the ASIP coding region does not play a central role in coat colour variation in cattle.

Agouti Signaling Protein↗
PubMed2006

Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene.

BACKGROUND: Phosphodiesterases are an important protein family that catalyse the hydrolysis of cyclic nucleotide monophosphates (cAMP and cGMP), second intracellular messengers responsible for transducing a variety of extra-cellular signals. A number of different splice variants have been observed for the human phosphodiesterase 9A gene, a cGMP-specific high-affinity PDE. These mRNAs differ in the use of specific combinations of exons located at the 5' end of the gene while the 3' half, that codes for the catalytic domain of the protein, always has the same combination of exons. It was observed that to deduce the protein sequence with the catalytic domain from all the variants, at least two ATG start codons have to be used. Alternatively some variants code for shorter non-functional polypeptides. RESULTS: In the present study, we expressed different splice variants of PDE9A in HeLa and Cos-1 cells with EGFP fluorescent protein in phase with the catalytic domain sequence in order to test the different start codon usage in each splice variant. It was found that at least two ATG start codons may be used and that the open reading frame that includes the catalytic domain may be translated. In addition the proteins produced from some of the splice variants are targeted to membrane ruffles and cellular vesicles while other variants appear to be cytoplasmic. A hypothesis about the functional meaning of these results is discussed. CONCLUSION: Our data suggest the utilization of two different start codons to produce a variety of different PDE9A proteins, allowing specific subcellular location of PDE9A splice variants.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Novel estrogen receptor beta transcript variants identified in human breast cancer cells affect cell growth and apoptosis of COS-1 cells.

Estrogen receptor (ER) beta gene codes for different transcript variants resulting from alternative splicing. In this study, we report identification of the two novel human exon-skipped ERbeta transcript isoforms ERbetaDelta125 and ERbetaDelta1256 in MDA-MD-231 breast cancer cells. Both transcripts could also be detected in a variety of human tissues. We further report the results of an in vitro attempt to characterize their function in regulation of cell growth, motility, apoptosis and gene expression. COS-1 cells stably transfected with the novel ERbeta transcripts exhibited a notably slower growth even in the absence of estradiol when compared to vector-transfected control cells. Like ERbeta1, both novel ERbeta transcript isoforms raised the basal apoptosis rate of COS-1 cells in a ligand-independent manner. Whereas introduction of ERbetaDelta1256 notably increased the sensitivity of COS-1 cells towards lower concentrations of selective estrogen receptor modulator tamoxifen, presence of ERbeta1 and ERbetaDelta125 transcripts further weakened the growth-inhibitory effect of tamoxifen on this cell line. Furthermore, expression of ERbetaDelta1256 variant was demonstrated to reduce transcript levels of estrogen-responsive genes like cyclin A2, IGFBP-4 and fibulin 1c in COS-1 cells in a ligand-independent manner. Though we were not able to detect the predicted 29 and 34kDa proteins by means of western blot analysis, our data strongly suggest the biological functionality of both isoforms on molecular level. With this report increasing the multitude of existing ERbeta mRNA isoforms, we provide further evidence that their synthesis has to be considered as an important level of estrogen signaling.

Alternative Splicing↗
PubMed2004

Functional characterization of Ih-channel splice variants from Apis mellifera.

We isolated splice variants of the AMIH cDNA by means of polymerase chain reaction and homology screening. Splicing at one site generates at least four different channel transcripts (AMIH, AMIHL, AMIHM and AMIHT), which code for ion-channel proteins that vary in the interloop regions between the membrane-spanning domains S4 and S5. HEK293 cells in which the AMIHL splice variants were functionally expressed generated currents that were activated by hyperpolarizing voltage steps. Compared to AMIH, AMIHL cells showed pronounced differences in the voltage dependency of activation: the incorporation of 32 extra amino acids between S4 and S5 shifts the activation curve by +25 mV. Intracellular cAMP made the current-activation potential still less negative and accelerated the activation more effectively than it does in AMIH cells. In vertebrates, functional diversity of Ih-channels is generated by four different genes. In Apis mellifera, splice variants coded by the single gene AMIH could generate a similar diversity.

Alternative Splicing↗