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PubMed1999

[Inheritance of pendulum movements in rats].

Inheritance of predisposition to pendulum movements (PMs) in rats was studied by two methods: segregation analysis of binary traits (on pedigrees recorded in the selection archives for cataleptic strain GC) and the classical Mendelian analysis of hybrids between strains PM+ and PM- selected for pronounced PMs and the absence of PMs, respectively. Both methods yields the same result: it was found that predisposition to PMs exhibited a monogenic dominant inheritance with incomplete penetrance.

Animals↗

PubMed1993

Genetico-mathematical analysis of the inheritance pattern of peptic ulcer disease. Direct methods of Weinberg. I. Method of probands and method of siblings.

Inheritance of ulcer disease was analyzed genetico-mathematically using two methods: the method of probands and the method of siblings. Families of 351 probands were enrolled in the study: 57 had type II and 27 type III gastric ulcer disease. 267 were with duodenal ulcer disease. The types of gastric ulcer were determined according to H. Johnson. A further 188 families of type I gastric ulcer probands were also studied. However, data from these are not included in the present study because our previous investigation has shown no genetic determination of this type of ulcer disease. The detailed segregation analysis employed in the study does not support the assumption of a monogenic type of disease inheritance. The values obtained for the coefficient of genetic proportion do not substantiate either autosomal-recessive or autosomal-dominant pattern of transmission. This refers both to ulcer disease in general and to the calculation of the coefficient depending on the type of disease and the type of familial predisposition of probands.

Bulgaria↗

PubMed1994

Family studies of non-insulin-dependent diabetes mellitus in South Indians.

Though a genetic basis for non-insulin-dependent diabetes mellitus (NIDDM) is clear, the likely mode of inheritance is not known. The segregation of NIDDM was studied in 64 nuclear South Indian pedigrees (449 individuals) ascertained through an affected proband having both parents and more than 1 sibling alive and available for oral glucose tolerance testing. A high proportion of parents were found to be of abnormal glucose tolerance [89 of 128 (70%) diabetic and 11 of 128 (9%) impaired]. Complex segregation analysis was performed using (1) POINTER which implements the mixed model and distinguishes major gene, multifactorial and non-transmitted environmental contributions to affection and (2) COMDS which implements an oligogenic model with major gene, modifier gene and environmental contributions to a) affection and b) diathesis (an ordered polychotomy amongst non-affected family members, based on 2-h plasma glucose level). Using POINTER, there was no formal support for a major gene and the most parsimonious solutions were achieved with multifactorial models. Using COMDS, we found i) significant improvements in models when information on glucose levels in nondiabetic family members (diathesis) was included, ii) support for segregation of a diallelic gene as well as background familial resemblance, and iii) under the best-supported model, this diallelic locus featured incomplete dominance (d = 0.8) and a disease-predisposing allele frequency of 14%. In South Indians, segregation of NIDDM is inadequately described by simple major gene models: more complex models provide more satisfactory descriptions. This finding, if applicable in other populations, has important implications for the search for diabetes-susceptibility genes.

Blood Glucose↗

PubMed1995

Genetic mapping and non-Mendelian segregation of mating type loci in the oomycete, Phytophthora infestans.

DNA markers linked to the determinants of mating type in the oomycete, Phytophthora infestans, were identified and used to address the genetic basis of heterothallism in the normally diploid fungus. Thirteen loci linked to the A1 and A2 mating types were initially identified by bulked segregant analysis using random amplified polymorphic DNA markers (RAPDs) and subsequently scored in three crosses polymorphisms (SSCP), cleaved amplified polymorphisms (CAPS), or allele-specific polymerase chain reaction markers (AS-PCR). All DNA markers mapped to a single region, consistent with a single locus determining both mating types. Long-range restriction mapping also demonstrated the linkage of the markers to one region and delimited the mating type locus to a 100-kb region. The interval containing the mating type locus displayed non-Mendelian segregation as only two of the four expected genotypes were detected in progeny. This is consistent with a system of balance lethal loci near the mating type locus. A model for mating type determination is presented in which the balanced lethals exclude form progeny those with potentially conflicting combinations of mating type alleles, such as those simultaneously expressing A1 and A2 functions.

Base Sequence↗

PubMed1999

Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families.

The aim of this study was to obtain evidence for the genetic basis of polycystic ovaries (PCO) and premature male pattern baldness (PMPB) by screening first-degree relatives of women affected by polycystic ovary syndrome (PCOS). Because of the high prevalence of PCO in the general population, we also studied first-degree relatives of ten asymptomatic control volunteers of reproductive age. The probands were recruited prospectively from infertility and endocrine clinics, where they presented with various clinical symptoms of PCOS. Each had PCO, on transvaginal ultrasound scan. The families of 29 probands and 10 volunteers agreed to take part in the study. Clinical, ultrasound, and biochemical parameters were used to define PCO/PCOS. All female relatives had an ovarian ultrasound scan and hormone profile performed. History was used to assign status in postmenopausal women. All male relatives were assessed for early onset (<30 yr old) male pattern baldness, by photographs. All relatives were assigned affected (PCO/PMPB) or nonaffected status, and segregation analysis was performed. Of the relatives of 29 PCOS probands, 15 of 29 mothers (52%), 6 of 28 fathers (21%), 35 of 53 sisters (66%), and 4 of 18 brothers (22%) were assigned affected status. First-degree female relatives of affected individuals had a 61% chance of being affected. Of the first-degree male relatives, 22% were affected. Of a total of 71 siblings of PCOS probands, 39 were affected, giving a segregation ratio of 39/32 (55%), which is consistent with autosomal dominant inheritance for PCO/PMPB. In the control families, 1 of 10 probands (10%), 1 of 10 mothers (10%), no fathers, 2 of 13 sisters (15%), and 1 of 11 brothers (9%) were affected. Of a total of 24 siblings, 3 were affected (13%), giving a segregation ratio (observed/expected) of 3/12, which was significantly different from autosomal dominant inheritance. The inheritance of PCO and PMPB is consistent with an autosomal dominant inheritance pattern in PCOS families, perhaps caused by the same gene. There was no such genetic influence in families of women without PCOS. Sisters of PCOS probands with polycystic ovarian morphology were more likely to have menstrual irregularity and had larger ovaries and higher serum androstenedione and dehydroepiandrosterone-sulfate levels than sisters without PCO. This suggests a spectrum of clinical phenotype in PCOS families. Men with PMPB had higher serum testosterone than those without. Collectively, these data are consistent with a role for genetic differences in androgen synthesis, metabolism, or action in the pathogenesis of PCOS.

Adult↗

PubMed1997

A biometrical study of the relationship between sodium-lithium countertransport and triglycerides.

We addressed the question: Is there evidence that allelic variation in a single unmeasured gene that has a large effect on maximal activity of erythrocyte sodium-lithium countertransport (Na-Li CNT) also has pleiotropic effects on variation in plasma triglyceride levels? Complex segregation analysis models that included plasma triglyceride levels as a covariate were considered as explanations for interindividual variation in Na-Li CNT. A sample of 711 healthy adults from 254 pedigrees enrolled in the Rochester Family Heart Study was selected for this study. The majority of the pedigrees supported the hypothesis that variations in a single unmeasured non-transmitted environmental factor have large effects on the Na-Li CNT distribution. Only gender-specific first-order covariate parameters were necessary in the complex segregation models suggesting that the form of the relationship between Na-Li CNT and plasma triglyceride level was not influenced by variation in the inferred environmental factor with large effects. Stratification of the sample by this inferred environmental factor resulted in three classes of individuals with significant differences in the distributions of coronary heart disease risk factor traits, as well as interindividual variation in both Na-Li CNT and plasma triglyceride levels. These results, along with other observations from the Rochester Family Heart Study sample, emphasize the complex and multifactorial nature of the causes of interindividual variation in Na-Li CNT. Our study further suggests that new research strategies are needed for studying the relationships between genetic and environmental variation and variation in quantitative traits such as Na-Li CNT that have been identified as risk factors for hypertension.

Adult↗

PubMed1975

Mapping of the immune response genes in the major histocompatibility complex of the Rhesus monkey.

Interest in the Ir genes of rheus monkeys stems from their phylogenetic relationship to man and the extensive data already available on the major histocompatibility complex of the monkey. At least two independent dominant H-linked Ir genes have been identified in the rhesus. These genes control the ability of monkeys to respond to the random linear copolymer of glutamyl alanine (GA), or the dinitrophenyl conjugate of glutamyl lysine (DNP-GL). These synthetic polymers can elicit weak delayed-type skin reactions and strong humoral responses in some monkeys. In a series of unrelated monkeys phenotyped for the serologically defined RhL-A specificities of both segregant series, there were no correlations between any RhL-A specificity and responder status to the GA or DNP-GL polymers. However, segregation analysis of 21 rhesus families sired by 3 fathers indicated the capacity of the offspring to form antibodies was associated with genes coded for in the RhL-A complex. In three monkeys, verified recombination within the RhL-A complex between the genes coding for the serologically defined determinants (SD loci) and the gene(s) controlling the lymphocyte-activating determinants (Lad loci) responsible for mixed lymphocyte reactivity was established. In two of these monkeys the immune response genes controlling the DNP-GL response segregated with the Lad genes, while in the third case the Ir-GL gene segregated with the SD loci, tentatively localizing the Ir-GL gene between the SD and Lad loci. In addition, we have shown that genetically distinct genes control responsiveness to DNP-GL and GA. These genes were separated by recombination, thus one monkey inherited the Lad, Ir-GL, and SD loci from one paternal haplotype and by crossing over inherited the gene controlling GA responsiveness from the other paternal haplotype. The fine structure mapping of the RhL-A gene complex is compared with the H-2 and HL-A gene complexes. Several striking similarities were noted.

Alanine↗

PubMed2005

Fine-mapping milk production quantitative trait loci on BTA6: analysis of the bovine osteopontin gene.

Bovine chromosome six (BTA6) harbors up to six quantitative trait loci (QTL) influencing the milk production of dairy cattle. In stark contrast to human, there is long-range linkage disequilibrium in dairy cattle, which has previously made it difficult to identify the mutations underlying these QTL. Using 38 microsatellite markers in a pedigree of 3,147 Holstein bulls, we fine mapped regions of BTA6 that had previously been shown to harbor QTL. Next, we sequenced a 12.3-kb region harboring Osteopontin, a positional candidate for the statistically most significant of the identified QTL. Nine mutations were identified, and only genotypes for the OPN3907 indel were concordant with the QTL genotypes of eight bulls that were established by segregation analysis. Four of these mutations were genotyped, and a joint linkage/linkage disequilibrium mapping analysis was used to demonstrate the existence of only two functionally distinct clusters of haplotypes within the QTL region, which were uniquely defined by OPN3907 alleles. We estimate a probability of 0.40 that no other mutation within this region is concordant with the QTL genotypes of these eight bulls. Finally, we demonstrate that the motif harboring OPN3907, which is upstream of the promoter and within a region known to harbor tissue-specific osteopontin regulatory elements, is moderately conserved among mammals. The motif was not retrieved from database queries and may be a novel regulatory element.

Alleles↗

PubMed2001

[Muscular dystrophies detected by immunophenotyping and genotype analysis (mRNA and DNA)].

Complex diagnosis of muscular dystrophies including clinical, bioptical and molecular genetic approaches has been provided in a limited extent in this country. Our group of neurologists, pathologists and geneticists has examined approximately 240 patients suspected of having muscular dystrophies, mostly coming from Southern and Northern Moravia. The patients were sent to the examination most often from departments of neurology and clinical genetics, and less frequently from departments of internal medicine. According to the final diagnosis, the patients were divided into groups: with dystrophinopathies and carriers of dystrophinopathies (DMD/BMD), merosin deficient form of congenital muscular dystrophy, and Emery-Dreifuss muscular dystrophy including the carriers of this disease. Some relatives of patients with dystrophinopathies were also examined using the methods of segregation analysis. High proportion of the DMD/BMD patients can be detected by the methods of molecular genetics. Analysis of mRNA using RT PCR and PTT enables the detection of deletions, duplications, and point mutations in dystrophin gene and encompasses a larger diagnostic scope in comparison with examinations of DNA level by the multiplex PCR method from the peripheral blood which enables only deletion detections. Immunophenotyping of the dystrophin protein plays an important role especially using antibodies against carboxyterminal (DYS2) and rod domain (DYS1) of dystrophin. Deficient sarcolemmal expression of DYS2 and DYS1 reveals unambiguously a pathological dystrophin. On the other hand, less pronounced deficiencies in dystrophin expression in BMD patients and DMD/BMD carriers may not always be detected in muscle biopsies. In this case, it is necessary to supplement the examination by Western blotting and genotype analysis. The examination of patients with clinically diagnosed muscular dystrophy should start with a muscle biopsy which enables the estimation of presence and degree of structural changes. Application of antibodies against the components of DGC and emerin may reveal a deficiency in expression of these proteins. Immunohistochemical examination completed by Western blotting leads to the subsequent molecular genetic analysis of DNA or mRNA. Secondary deficiencies in expression of other DGC proteins are often revealed in muscle biopsies of dystrophinopathies and this fact must be taken into account in the evaluation of immunohistochemical findings. There is a possibility of replacement of invasive muscle biopsy by skin biopsy or buccal mucosal smears in cases of merosin and emerin deficiencies. Commercially available antibodies against merosin, emerin, calpain and sarcoglycans enable extensive identification and detailed classification of muscular dystrophies. Screening of the patients based on the application of methods described and discussed in this report is the task of the forthcoming period.

Adolescent↗

PubMed1996

Natural translocation of a large segment of chromosome III to chromosome I in a laboratory strain of Saccharomyces cerevisiae.

We have investigated chromosomal segregation during meiosis in a cross between two polymorphic haploid laboratory strains of Saccharomyces cerevisiae, FL100 and GRF18. These two strains have large chromosome-length polymorphisms for chromosomes I and III allowing for easy scoring of parental chromosomes after meiotic segregation. Chromosome III in the FL100 strain was 35 kb shorter than chromosome III in GRF18, while FL100 chromosome I was 40 kb larger than chromosome I in GRF18. Segregation analysis of chromosomes I and III in 50 tetrads showed an apparent association between chromosomes I and III, whereas only the original parental association of chromosomes I and III was found in the spores. By hybridization with chromosome-specific probes we have shown that the polymorphisms are due to a large translocation from chromosome III onto chromosome I in FL100. The translocated fragment is larger than 80 kb and was mapped between Ty and HML. In nine tetrads analyzed, chromosome-length polymorphisms which did not segregate according to Mendelian law were observed.

Blotting, Southern↗

PubMed2026

A novel missense mutation in tropomyosin 1 gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder that can lead to heart failure or sudden death. Family-based identification of rare sarcomeric variants can support molecular diagnosis and cascade screening in inherited HCM. This study aimed to identify and evaluate a novel TPM1 variant found in a Vietnamese family with HCM. The proband, a 3-year-old boy diagnosed with HCM, and eight relatives from three generations underwent clinical and genetic evaluation. A candidate variant initially identified by targeted next-generation sequencing was validated by PCR and Sanger sequencing. Familial segregation analysis was performed, and variant pathogenicity was assessed according to ACMG guidelines with support from in silico prediction and structural modeling. Sanger sequencing confirmed a heterozygous missense variant in exon 6 of TPM1 NM_001018005.2:c.576G > C, p.(Glu192Asp), in the proband, his father, and paternal grandfather, all of whom exhibited clinical signs of HCM. The variant was absent in unaffected relatives and in public population databases. Based on ACMG criteria (PM1, PM2, PM5, and PP3), the variant was classified as likely pathogenic. This novel TPM1 variant segregated with HCM in a Vietnamese family, expands the known mutational spectrum of TPM1 in hypertrophic cardiomyopathy, and warrants further functional investigation and familial genetic evaluation.

American College of Medical Genetics and Genomics ↗

PubMed1986

Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae.

The cell division cycle of the yeast Saccharomyces cerevisiae is triggered at the stage called 'START'. Many results strongly suggest that adenylate cyclase is an essential element of the control of START. We report here results arguing for a positive control of the cAMP level by the CDC25 gene, another gene of START. Firstly, cdc25 cells can be rescued by extracellular cAMP. Secondly, the cellular cAMP content drops when thermosensitive cdc25 mutant cells are shifted to restrictive temperature. We report the molecular cloning of the CDC25 gene by complementation of cdc25 mutant cells. The identity of the cloned gene was confirmed by site-specific gene re-integration experiments and segregation analysis: the isolated fragment is shown to integrate into the cdc25 gene locus. When transferred in cdc25 mutant cells this DNA prevents the drop of the cAMP level at restrictive temperature. This gene is transcribed in a 5200-nucleotides mRNA. We have determined the nucleotide sequence of a 5548-bp DNA fragment which shows an uninterrupted open reading frame (ORF) coding for a 1587-amino acid polypeptide chain. Only the C-terminal part of the ORF appears to be essential for the complementation of the cdc25-5 allele, suggesting a multidomain protein.

Alleles↗

PubMed1994

Regional assignment of a human DNA repair gene (XRCC5) to 2q35 by X-ray hybrid mapping.

A number of human genes involved in the repair of radiation-induced DNA double-strand breaks have been identified based on the analysis of radiation-sensitive rodent mutants. Recently, one of the DSB repair genes, XRCC5, has been mapped on human chromosome 2 by concordance analysis of somatic cell hybrids and by the microcell-mediated chromosome transfer approach. For the regional mapping of the human XRCC5 gene, we have constructed a panel of X-ray hybrids and a panel of microcell-mediated chromosome 2 hybrids in the mutant background that contain only fragments of human chromosome 2. By using fluorescence in situ hybridization, chromosome banding, and physical mapping of these X-ray hybrids, we have localized the human XRCC5 locus to 2q35. This result is further confirmed by a segregation analysis indicating that the radiation resistant phenotype of a repair-proficient hybrid cosegregates with the human 2q35 chromosome fragment.

Animals↗

PubMed2000

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Adult↗

PubMed2001

Familial aggregation of QT-interval variability in a general population: results from the NHLBI Family Heart Study.

QT-interval prolongation is associated with increased risk of cardiac death. Although information on genetics and molecular mechanisms of the congenital long QT syndrome is mounting, limited data are available on the genetics of QT interval in the general population. Heart rate adjusted QT intervals (Bazett's QTc, and QT index (QTI)) were assessed by electrocardiography in 2399 members aged 25-91 years of 468 randomly selected families participating in the NHLBI Family Heart Study. Familial correlation and segregation analyses were performed to evaluate the genetics of the variability of QT interval in this population. The parent-offspring (0.14+/-0.03) and sibling (0.18+/-0.03) correlations for age and sex-adjusted QTc were moderate, while the spouse correlation was close to zero (0.09+/-0.06). This suggests that there are familial/genetic influences on QT-interval variability. Segregation analysis results suggest that there is a major effect in addition to heritable multifactorial effects (h2=0.34), but the major effect did not follow Mendelian inheritance. Further adjustments of QTc for other major cardiovascular risk factors did not significantly change the results. Similar results were found for QTI. The QT-interval variation in the general population is influenced by moderate heritable multifactorial effects in addition to a major effect. A major gene effect is not directly supported.

Adult↗

PubMed2003

Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.

Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend.0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.

Adult↗

PubMed1994

Enhanced frequency of transposition of the maize transposable element Activator following excision from T-DNA in Petunia hybrida.

Many of the systems currently employed for heterologous transposon tagging in plants rely on an excision assay to monitor transposon activity. We have used the streptomycin phosphotransferase (SPT) reporter system to assay Ac activity in Petunia hybrida. In other species, such as tobacco or Arabidopsis, excision of Ac from the SPT gene in sporogenous tissue gives rise to streptomycin-resistant seedlings in the following generation. The frequency of fully streptomycin-resistant seedlings in petunia was low (0.4%) but molecular analysis of these indicated that the actual excision frequency may be as low as 0.05%. This indicates that the SPT assay is not a reliable selection criterion for germinal excision in petunia. Extensive molecular screening for reinsertion of Ac was consistent with a low primary transposition frequency (0%-0.6%). In contrast to these findings, the progeny of confirmed germinal transpositions for three independent transformants showed frequent transposition to new sites (9.5%-17.0%). This suggests a high frequency of secondary transposition compared with primary transposition from the T-DNA. Segregation analysis indicates that the high transposition activity is closely associated with transposed copies of Ac. No evidence was found for an altered methylation state for Ac following transposition. The implications of these results for heterologous transposon tagging in petunia are discussed in the context of the reliability of excision reporter systems in general.

DNA Repair↗

PubMed1997

Quantitative genetic analysis of arterial oxygen saturation in Tibetan highlanders.

This study was designed to test the hypothesis that genetic differences inferred from biological kinship relationships among individuals contribute to individual variation in percentage of oxygen saturation of arterial hemoglobin (SaO2) in a high-altitude native population. SaO2 data were obtained by pulse oximetry from 354 nonpregnant, healthy Tibetan residents of Pen-Dri, two rural agropastoral villages at 3800-4065 m altitude in Lhasa Municipal District, Tibet Autonomous Region, China. Statistical analyses of these data from 46 pedigrees tested the hypothesis of a significant genetic contribution to SaO2 variation. The average SaO2 was 89.4 +/- 0.2%, with a range of 76-97%. Additive genetic effects account for 44% of the interindividual phenotypic variation in SaO2 in the sample. Complex segregation analysis and variance decomposition analysis determined that 21% of the total phenotypic variation could be explained by a major gene influencing SaO2. Homozygotes for the low-SaO2 allele have a mean SaO2 of 83.6%, whereas heterozygotes and homozygotes for the high-SaO2 allele have means of 87.6% and 88.3%, respectively. This confirms findings in another Tibetan sample and extends the known geographic distribution of the major gene. These results suggest the hypothesis that individuals with the dominant allele for higher SaO2 have a selective advantage in their high-altitude hypoxic environment.

Adaptation, Physiological↗