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PubMed1986

Response of the coronary artery to a small dose of ergonovine in variant angina.

The response of the coronary artery to a small dose (0.01 mg) of ergonovine was observed in nine patients without variant angina and in 10 patients with variant angina. Coronary angiograms were obtained before and after small and larger (routinely used) doses of ergonovine. With the larger dose, all 10 patients with variant angina had total or subtotal spastic occlusion accompanied by angina and ECG changes. Excluding the site of spastic occlusion produced by the larger dose of ergonovine, diameters of proximal, middle, and distal segments in each major coronary artery were measured before and after a small dose of ergonovine. The mean percentage of change in diameter (diameter before - diameter after a small dose of ergonovine)/diameter before a small dose of ergonovine X 100% in patients without variant angina was not significantly different from that in patients with variant angina (5.2 +/- 9.5% vs 7.0 +/- 11.9%, respectively). However, in patients with variant angina, a small dose of ergonovine produced a percentage of change in diameter of 39.8 +/- 15.3% at the site of spastic occlusion included by a larger dose of ergonovine, compared with that of 7.0 +/- 11.9% in the remaining non-spastic coronary arteries (p less than 0.05). These results indicate that patients with variant angina have local segments which respond differently to ergonovine from the remaining segments of coronary arteries. Clinically, this observation might be helpful in determining the angiographic positivity to ergonovine.

Adult↗

PubMed1997

Soluble E-selectin, ICAM-1 and VCAM-1 levels in systemic and coronary circulation in patients with variant angina.

OBJECTIVE: The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation. METHODS: Antecubital venous plasma samples were collected from 33 patients with variant angina, 22 patients with stable effort angina and 20 control subjects. Samples were also collected from the aortic root (AO) and the coronary sinus (CS) in 18 patients with variant angina before and after left coronary spasm induced by intracoronary injection of acetylcholine. The soluble adhesion molecules were assayed by enzyme immunoassay. RESULTS: Antecubital venous plasma soluble E-selectin (P < .05), ICAM-1 (P < .01) and VCAM-1 (NS) levels were higher in the variant angina group than in the control group, respectively. The plasma soluble ICAM-1 level was also higher (P < .01) in the variant angina group than in the stable effort angina group. In the variant angina group, both soluble ICAM-1 (P < .05) and VCAM-1 (P < .01) levels were significantly lower in CS than AO at baseline. In contrast, after the spasm the plasma soluble ICAM-1 level was (P < .05) higher in CS than AO and the CS-AO differences of soluble ICAM-1 (P < .05) and VCAM-1 (P < .05) increased as compared with the baseline, respectively. These values were remained unchanged in the stable effort angina group after rapid atrial pacing and in the control group after administration of acetylcholine. CONCLUSIONS: Circulating plasma levels of both soluble E-selectin and ICAM-1 were elevated in patients with variant angina, indicating an association of an inflammatory reaction with coronary spasm. Both soluble ICAM-1 and VCAM-1 appeared to be trapped in the coronary circulation at baseline and released into the coronary circulation following coronary spasm and reperfusion in the patients.

Acetylcholine↗

PubMed1989

Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates.

Antigenic variation of African trypanosomes results from the periodic activation of a single new variant cell surface glycoprotein (VSG) gene out of a repertoire of about a 1000 VSG genes. In spite of the apparently random genetic basis of the process of antigenic variation, the relapsing parasitemias are characterized by an as yet unexplained order of appearance of major VSG variants. Here we mathematically test hypotheses concerning the blood-based parasitemia. In our model the antigenic switches occur at random at the DNA level. A variable proportion of the switches has a short intermediate phase in which two different VSGs simultaneously occur on the cell surface. We show that, in a theoretical population of 230 single expressor variants in an immunocompetent or in an immunodeficient host, it is not possible to explain the ordered appearance of variants by affecting the growth coefficients of single expressors or double expressors or by affecting the antigen switch probabilities. Rather, a realistic parasitemia can be obtained if the majority of switches has a double expressor switch-intermediate phase and if the double expressors have a differential susceptibility to the immune control. This study is significant in providing a theoretical basis for the ordered appearance of variants and in explaining previously unresolved discrepancies between the rate of appearance of new variants in culture and in vivo. In addition, testable predictions as to the development of the infections, switch rate of variants, fraction of double expressors, and parasite mortality coefficients are generated.

Animals↗

PubMed1998

Determination of the disulfide bonds within a B domain variant surface glycoprotein from Trypanosoma congolense.

The disulfide bonds within a variant surface glycoprotein from Trypanosoma congolense have been determined. L-[35S]Cysteine metabolically labeled protein was digested with trypsin, and radiolabeled peptides were separated by reversed-phase high performance liquid chromatography, and putative cystine-containing peptides were subdigested with other proteases and analyzed after further purification by amino acid sequencing and mass spectrometry. All eight cysteine residues of the protein, located within the N-terminal domain, are covalently linked. The four disulfide bonds are between cysteines 16/236, 171/193, 195/206, and 286/298. This is, for the first time, the determination of disulfide bonds within a variant surface glycoprotein belonging to the B-type. As all the eight cysteines of BENat 1.3 variant surface glycoprotein are positionally conserved, the cystine pattern of this protein can be regarded as a prototype of disulfide bonding within B-type variant surface glycoproteins. Although the cysteine residues of B-type variant surface glycoproteins are located at completely different positions in the protein chain compared with A-type variant surface glycoproteins, the positions of the disulfide bonds can easily be integrated into the A-type tertiary structure. This result implies that, despite their enormous amino acid sequence variability, variant surface glycoproteins, regardless of their subtype, can fold into a similar tertiary structure.

Amino Acid Sequence↗

PubMed2026

Biallelic ABCA13 Loss-of-Function Variants in a Child With Neurodevelopmental Delay: A Case Report.

ABCA13 encodes ATP-binding cassette subfamily A member 13, one of the largest members of the ABC transporter family. Rare ABCA13 variants have been reported in neuropsychiatric and neurodevelopmental phenotypes, including schizophrenia, bipolar disorder, autism spectrum disorder, intellectual disability, and developmental delay; however, the mode of inheritance remains uncertain, and most published cases have focused on heterozygous variants in the context of a possible dominant or susceptibility model. We report a 5-year-old boy with neurodevelopmental delay, skeletal foot deformities, nonspecific dysmorphic features, convergent strabismus, and behavioral abnormalities. Initial genome sequencing analysis was nondiagnostic. Reanalysis after 6 months identified two rare predicted loss-of-function variants in ABCA13 in trans: c.2510del, p.(Leu837TyrfsTer21), a frameshift variant, and c.12064C>T, p.(Arg4022Ter), a nonsense variant previously reported in a patient with unexplained intellectual disability. The identification of compound heterozygous predicted loss-of-function variants supports the possibility that biallelic disruption of ABCA13 may contribute to neurodevelopmental disease, whereas previously reported heterozygous variants may represent incompletely penetrant risk alleles, susceptibility factors, or candidate findings rather than fully penetrant dominant causes. This case expands the emerging clinical and genetic spectrum associated with ABCA13 and supports further evaluation of a recessive model in patients with intellectual disability and neurodevelopmental delay.

ABCA13↗

PubMed2024

SLC12A1 variant c.1684+1 G>A causes Bartter syndrome type 1 by promoting exon 13 skipping.

BACKGROUND: Bartter syndrome type 1, an autosomal recessive genetic disorder, is caused by pathogenic loss-of-function variants in the SLC12A1 gene. It is characterized by metabolic alkalosis and prenatal-onset polyuria leading to polyhydramnios. METHODS: We identified pathogenic gene in a 12-day-old newborn boy with Bartter syndrome type 1 using whole-exome sequencing. Sanger sequencing validated the identified variants. A minigene assay was performed to investigate the effect of a novel splice site variant on pre-mRNA splicing. RESULTS: We found a compound heterozygous variants in the SLC12A1 gene, consisting of a known pathogenic missense mutation (NM_000338: c.769 G>A; p.Gly257Ser) and a novel splice site variant (c.1684+1 G>A). In silico predictions and an in vitro minigene splicing assay demonstrated that the splicing variant c.1684+1 G>A abolished a consensus splice donor site of SLC12A1 intron 13, resulting in complete exon 13 skipping, translational frameshift, and premature termination codon, ultimately leading to loss of SLC12A1 function. CONCLUSION: Using a cell-based in vitro assay, we revealed the aberrant effect of the pathogenic splicing variant SLC12A1 c.1684+1 G>A on pre-mRNA splicing. Our findings expand the gene mutation spectrum of Bartter syndrome type 1, providing a basis for genetic diagnosis and the development of genetic medicines.

Humans↗

PubMed1999

Limited efficacy of magnesium for the treatment of variant angina.

Some patients with variant angina show both ST segment elevation at rest and exercise-induced ST segment elevation. Magnesium deficiency has also been observed in patients with variant angina. This study investigated the correlation between the degree of magnesium deficiency and the efficacy of intravenous administration of magnesium in patients with variant angina. Fifteen patients with angiographically confirmed variant angina were assessed for magnesium deficiency and whether intravenous administration of magnesium (19.2 mEq/l) suppressed exercise-induced ST segment elevation. All 15 patients were studied with a magnesium retention test (0.2 mEq/kg over 4 hr) to analyze magnesium deficiency. In our study, magnesium retention rate in patients with variant angina was not higher than that of controls (57 +/- 24% vs 45 +/- 10%, NS). All 15 patients had anginal attacks during accelerated exercise combined with hyperventilation after placebo infusion, whereas only 8 patients had anginal attacks after magnesium administration. ST segment elevation occurred in 14 patients after placebo infusion, but in only 4 patients after magnesium administration. There were no correlations between disease activity, degree of magnesium deficiency or failure of suppression of ST elevation by the intravenous administration of magnesium. Intravenous administration of magnesium can suppress exercise-induced coronary spasms in some patients with variant angina, but the degree of magnesium deficiency did not correlate with the suppressions of exercise-induced ST elevation after magnesium administration. Intravenous administration of magnesium had limited efficacy in patients with variant angina and exercise-induced ST segment elevation.

Acetylcholine↗

PubMed2026

Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease.

BACKGROUND: Orofacial clefts (OFCs) and other palate abnormalities (PAs) are among the most common birth defects worldwide and are characterized by the abnormal formation of the lip and/or palate. Genetic studies have traditionally classified OFC cases as either syndromic, involving OFCs alongside other congenital anomalies, or nonsyndromic, which represent the majority of cases and occur in isolation. Emerging genomic evidence indicates that genes traditionally associated with syndromic forms of OFC can also harbor variants contributing to isolated cases, challenging the notion of a strict dichotomy between these categories and supporting their integration for gene discovery. METHODS: In this study, we applied multiple analytic approaches to characterize the genetic architecture of OFC and PAs by integrating genomic data from 2,497 trios with probands diagnosed with an OFC (n=2,080) or PA (n=417). We compared these findings across OFC subtypes and syndromic status with those from 5,515 control trios to identify enriched biological pathways and mechanisms and to prioritize candidate genes using variant burden testing. RESULTS: We observed a significant enrichment of de novo protein-truncating and damaging missense variants in cases compared to controls (OR = 2.17, p = 1.21×10-32), with particularly strong signals in biologically relevant gene sets involving OFC-associated, constrained, Mendelian disorder, and mouse candidate genes. Variant burden testing identified 39 OFC risk genes at FDR ≤ 0.05, which we then integrated with 593 established OFC genes to interrogate the functional underpinnings of OFC via network analysis. This analysis revealed 309 high-order interactor genes not previously associated with OFC. Notably, this OFC network clustered into ten distinct biological pathways, with nucleosome-associated genes showing significant enrichment among cases in our cohort (OR = 14.8, p = 8.1×10-4). In a final integrative step, we combined evidence across all analyses to nominate 231 candidate genes, 32 of which contained at least two deleterious de novo variants in our cohort. CONCLUSIONS: These findings underscore the value of integrating diverse OFC and PA subtypes, syndromic status, and variant classes to elucidate the genetic architecture of these disorders, highlighting both phenotypic expansion of known disease genes and the emergence of novel gene-phenotype associations.

De Novo Variant Enrichment↗

PubMed1995

Trichoblastic fibroma. A series of 10 cases with report of a new plaque variant.

BACKGROUND: Trichoblastic fibroma is a benign trichogenic tumor that has both epithelial and mesenchymal components and exhibits partial to complete follicular induction. We studied 10 cases of trichoblastic fibroma and reviewed their clinical and histologic features. OBSERVATIONS: All 10 tumors were located on the face. Nine of 10 patients were women. The mean age at presentation was 63.8 years (range, 35 to 81 years). Two distinct subsets of trichoblastic fibroma were identified: the nodular variant and the plaque variant. The nodular variant is well circumscribed, while the plaque variant is poorly circumscribed, has significant subclinical extension, and may represent the low-grade malignant counterpart of the classic nodular trichoblastic fibroma. Histologically, both variants demonstrate mesenchymal induction with keratin cysts, papillary mesenchymal bodies, and an inductive fibroblastic stroma. CONCLUSIONS: Trichoblastic fibroma may be confused clinically and/or histologically with basal cell carcinoma. Identification of the mixed epithelial-mesenchymal components is helpful in tumor recognition. The plaque variant trichoblastic fibroma has not been previously reported. Familiarity with this variant is important because of the potential for infiltrative growth.

Adult↗

PubMed1999

Selection of genetic variants of the 5' noncoding region of hepatitis C virus occurs only in patients responding to interferon alpha therapy.

Interferon alpha (IFN alpha) can suppress the replication of hepatitis C virus (HCV) in chronically infected patients. However, HCV persists in a significant number of patients despite the normalization of alanine transaminase (ALT) during IFN alpha therapy. In this study, HCV variants in patients under IFN alpha therapy were characterized to examine their role in viral persistence during the therapy. Sixteen patients selected for this study were infected with HCV genotype 1b and remained HCV RNA positive for at least 1 month after onset of therapy. Nine patients responded to the therapy in terms of normalization of ALT (responders), whereas seven patients did not show a significant decrease of ALT level (nonresponders). To examine HCV populations in these patients, the HCV 5' noncoding region (5' NCR) was analyzed by polymerase chain reaction amplification and sequencing. Newly emerging variants of the HCV 5' NCR replaced predominant variants present prior to IFN alpha therapy in six of nine responders. Most predominant HCV variants during IFN alpha therapy carried a nucleotide substitution G to A at nt 231 within the 5' NCR. An analysis of the HCV quasispecies population in one responder revealed that a preexisting variant became predominant under IFN alpha therapy. These results emphasized the importance of the genetic heterogeneity of the HCV genome for viral resistance to IFN alpha. Five of seven HCV isolates from nonresponders were identical to those found in responders with regard to the nucleotide sequence of the 5' NCR. However, no selection of variants of the HCV 5' NCR occurred in nonresponders during the course of therapy. We conclude that IFN alpha treatment leads to the selection of variants of the HCV 5' NCR only in responders and may act differently in nonresponders. Our results suggest that the HCV 5' NCR may be a target of anti-HCV actions of IFN alpha.

5' Untranslated Regions↗

PubMed1998

Dominant expression of sex-hormone-binding-globulin exon-7 splicing variant over wild-type mRNA in human ovarian cancers.

The intracellular expression of sex-hormone-binding-globulin(SHBG) exon-7-splicing-variant mRNA in human ovarian cancers was demonstrated by reverse-transcription/polymerase-chain-reaction, Southern-blot and DNA-sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon 7, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of this variant might be different from that of the SHBG wild type. SHBG wild-type and variant mRNA was detected in all normal ovaries and in benign and malignant ovarian tumors analyzed. There were no significant differences in mean SHBG wild-type and variant mRNA levels among the 3 types of tissue, but the ratio of SHBG exon-7-splicing-variant to wild-type mRNA level in ovarian cancers was significantly higher (p < 0.05) than that in normal ovaries, with over-expression in some benign tumors. SHBG mRNA levels and the ratio of SHBG variant to wild-type mRNA was not associated with histological classification or clinical stages of ovarian cancers. These results suggest that over-expression of SHBG-exon 7-splicing-variant mRNA to the wild type might indicate the potential for neoplastic transformation.

Blotting, Southern↗

PubMed1996

Homologous recombination in variants of the B16 murine melanoma with reference to their metastatic potential.

Genomic instability has been accepted as providing a phenotypic variety of malignant cells within a developing tumour. Defects in genetic recombination can often lead to phenotypic differences; therefore, it is possible that metastatic variant cell lines exhibit their particular phenotype as a result of an altered ability to catalyse homologous recombination. We have investigated recombination efficiency in B16 melanoma metastatic variants, using a plasmid, pDR, as a recombination substrate. The plasmid contains two truncated, nontandem but overlapping segments of the neomycin resistance gene (neo 1 and neo 2), separated by the functional gpt gene unit. Only a successful recombination of the two neo segments will generate a functionally intact neomycin gene. Extrachromosomal recombination here was a transient measure of the cells to recombine the neo fragments in an intra- or intermolecular manner. Extrachromosomal recombination frequencies were higher in the high metastasis variants (BL6, ML8) compared with the low metastatic F1 cells. On the other hand, the frequency of chromosomal recombination (after plasmid integration) was higher for the low metastasis (F1) cell line compared with the highly metastatic variants, BL6 and ML8. Since the recombination assay measures only successful recombination events, we have interpreted the observed higher incidence of chromosomal recombination in the low metastatic variant line as indicative of a more stable genome. Similarly, a higher inherent instability in the genome of the high metastasis variants would render these less efficient at producing and maintaining successful recombination events, and this was found to be true by Southern analysis. The results presented show that frequency of recombination may be adduced as evidence for implicating genomic instability in the generation of variant cell populations during metastatic spread. Such an interpretation is also compatible with the Nowell hypothesis for tumour progression.

Animals↗

PubMed1997

Effect of heat shock treatment on the production of variant testosterone-repressed prostate message-2 (TRPM-2) mRNA in culture cells.

The testosterone-repressive prostate message-2 (TRPM-2) variant mRNA lacking the exon 5 was induced in rat primary culture hepatocytes by heat shock treatment. A similar variant mRNA lacking exon 5 was also induced by heat shock treatment of the human culture cell line HepG2. On the other hand, in mouse cell line L929, heat shock treatment induced a variant TRPM-2 mRNA lacking only a small region located in exon 5. However, irrespective of the difference of mechanism of variant production, all the variant TRPM-2 mRNA species derived from each animal species encoded a putative protein constituted from the N-terminal one-third of TRPM-2 protein attached to a C-terminal TRPM-2 unrelated tail. In humans, the variant TRPM-2 species was not detected in normal tissues but was present in certain kinds of tumour cells. These results indicate that the splicing variants were induced as a direct result of heat shock treatment on cells per se and that the phenomenon of heat shock induction was observed in culture cells derived from different animal species.

Alternative Splicing↗

PubMed1987

Unique variants of hCG in sera of choriocarcinoma patients.

Human chorionic gonadotropin (hCG) of pregnancy can be separated into several variants by an isoelectric focusing (IEF) method. The hCG produced by choriocarcinoma consists of components found in pregnancy sera (pI 3.9-6.0) and, in addition, unique variants with more acidic isoelectric points ranging from 3.2 to 3.7. The sera of all five patients with advanced choriocarcinoma contained these unique acidic variants of hCG and the immunoreactive levels were significantly higher in these patients than in normal pregnant women or patients afflicted with hydatidiform mole or invasive mole. When the acidic variants of hCG were treated with neuraminidase they migrated to the alkaline region (pI 9-11) of the IEF column. In conclusion, sera of choriocarcinoma patients contain unique variants of hCG. The finding that these highly acidic components can be converted to molecules with an alkaline pI by neuraminidase digestion suggests that this high negative charge may be due to an increased sialic acid content. Patients possessing the acidic variants of hCG in their sera had poor survival rate. Determination of the variants may be useful as a prognosis marker and in evaluating the efficacy of therapy.

Chorionic Gonadotropin↗

PubMed2002

Association studies of the HOPA dodecamer duplication variant in different subtypes of autism.

The HOPA gene in Xq13 is coding for a protein involved in a nuclear thyroid receptor complex. Previous studies suggested association of the dodecamer duplication in the OPA-repeat region in exon 43 (according to the genomic database sequence) with autism, mental retardation, and schizophrenia/hypothyroidism. We determined the frequency of this 12 bp duplication variant in a sample of 155 patients divided in different subtypes of autism, 278 parents of those patients, and 157 control individuals. The allele frequency of the duplication variant was not significantly different between autistic patients, their parents, and the control group. Therefore, it is unlikely that this 12 bp duplication variant of the HOPA gene has major relevance to the susceptibility to different subtypes of autism at least in this German patient sample. In addition, we identified a third variant with a 15 bp deletion in the OPA-repeat region, recently described by another group, in one autistic patient. This third allele was also present in the patient's nonautistic mother and sister, who are heterozygous for this variant, but could not be detected in any other individual genotyped in this study. Expression analysis revealed transcription of all three allelic variants in lymphoblastoid cell lines. Furthermore, we identified a new splice variant that utilizes an additional 9 bp of the 3' intron subsequent to exon 39. Both alternative transcripts are coexpressed in all fetal and adult tissues examined.

Alternative Splicing↗

PubMed2026

Genetic Ancestry and Carrier Variant Frequency Enrichment in a Colombian Andean Population: Insights From the Eje Cafetero.

Colombia is one of the most genetically diverse populations in Latin America, and its demographic process has promoted the persistence and local enrichment of deleterious alleles, increasing the frequency of autosomal recessive disorders, particularly in semi-isolated Andean populations such as the Eje Cafetero. However, exome-based reference data from this region remain scarce, limiting ancestry-aware variant interpretation and carrier screening strategies. We aimed to characterize the ancestry proportions of this population using exome data, and to estimate the carrier frequency and distribution of pathogenic and likely pathogenic (P/LP) variants in clinically relevant recessive genes. We conducted a cross-sectional study with whole-exome sequencing (WES) in 316 unrelated individuals from the Colombian Eje Cafetero. P/LP variants were evaluated in 454 genes associated with autosomal recessive disorders. The global ancestry proportions were estimated using a validated panel of 250 exome-compatible ancestry-informative markers. Carrier frequencies were compared against Non-Finnish Europeans (NFE) and Admixed Americans (AMX) from gnomAD v4. The cohort showed predominant European ancestry (mean 51%), followed by Native American (36%) and African (13%) components. We identified 151 carriers of 89 distinct pathogenic variants across autosomal recessive genes. The most frequent variants were SERPINA1 c.863A>T (5.5%), CFTR c.1210-11T>G (3.5%), and PYGM c.1094C>T (1.5%). Also, recurrent variants were significantly enriched compared with both NFE and AMX populations, supporting regional founder effects. This study represents one of the most comprehensive exome-based genetic characterizations of the Colombian Eje Cafetero, revealing ancestry-specific enrichment of clinically relevant autosomal recessive variants driven by founder effects.

Female↗

PubMed2005

Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2).

We report a possible association between autism in our sample and a recently described brain-expressed tryptophan hydroxylase gene (TPH2). The well-replicated involvement of the serotonin neurotransmitter system in autism has stimulated interest in many genes in the serotonin pathway as possible candidates for mutations leading to autism susceptibility. Serotonin synthesis is controlled by the rate-limiting enzyme tryptophan hydroxylase. A mouse study of the original tryptophan hydroxylase gene (TPH1) and the new isoform (TPH2) showed that while TPH1 is primarily expressed peripherally, TPH2 is found exclusively in brain tissue. We searched for human sequence variants in 6,467 nucleotides covering all 11 exons of TPH2, and also 248 nucleotides upstream of the start codon, and 935 nucleotides downstream of the stop codon. Eighteen variants were characterized in 88 subjects with autism studied at our two centers, and 95 unrelated control subjects. Using a model-free association method and empirical P value estimation, two variants showed frequency differences between autism and control subjects (P = 0.01 for a T-G variant in intron 1, and P = 0.02 for a A-T variant in intron 4). A haplotype including these variants showed slightly increased significance (P = 0.005). Further investigation of clinical phenotypes showed a possible association between presence of the variants at these two SNPs and higher scores on the Autism Diagnostic Interview (ADI) domain describing repetitive and stereotyped behaviors (P = 0.007). We conclude that TPH2 may play a modest role in autism susceptibility, perhaps relating specifically to repetitive behaviors, pending replication of this result.

Autistic Disorder↗

PubMed1978

Distribution of albumin variants Naskapi amd Mexico among Aleuts, Frobisher Bay Eskimos, and Micmac, Naskapi, Mohawk, Omaha, and Apache Indians.

In order to help define the boundaries of the distribution of the albumin variants Naskapi and Mexico which are polymorphic among several American Indian groups, we examined sera from Micmac, Mohawk, Northwest River Naskapi, Omaha and Apache Indians, and from Aleuts and Eskimos. Sera from a total of 1,524 individuals were examined. Using a cellulose acetate membrane electrophoretic system with Tris-Citric acid at pH 5.4 we were able to distinguish normal albumin and both variants in the same run. Naskapi and Mexico variants were absent from Aleut, Eskimo, Micmac, Mohawk and Omaha samples. The albumin Naskapi variant was present in an allele frequency of 0.03 in the Naskapi Indian sample. Albumin variants Naskapi and Mexico were found in the Apache sample at frequencies of 0.016 and 0.037, respectively. This report supersedes that previously published by Schell and Agarwal ('76). Generally, within an area there is a correspondence between changes in the frequency of albumin variants and changes in the ethnic background and history of the area's populations. At the same time, when viewing widely separated areas, relationships between distant groups based on linguistic and cultural similarities are paralleled on a biologic level by the distribution of normal albumin and variant albumins.

Alleles↗