Estimating the genome-wide contribution of selection to temporal allele frequency change.

Rapid phenotypic adaptation is often observed in natural populations and selection experiments. However, detecting the genome-wide impact of this selection is difficult since adaptation often proceeds from standing variation and selection on polygenic traits, both of which may leave faint genomic signals indistinguishable from a noisy background of genetic drift. One promising signal comes from the genome-wide covariance between allele frequency changes observable from temporal genomic data (e.g., evolve-and-resequence studies). These temporal covariances reflect how heritable fitness variation in the population leads changes in allele frequencies at one time point to be predictive of the changes at later time points, as alleles are indirectly selected due to remaining associations with selected alleles. Since genetic drift does not lead to temporal covariance, we can use these covariances to estimate what fraction of the variation in allele frequency change through time is driven by linked selection. Here, we reanalyze three selection experiments to quantify the effects of linked selection over short timescales using covariance among time points and across replicates. We estimate that at least 17 to 37% of allele frequency change is driven by selection in these experiments. Against this background of positive genome-wide temporal covariances, we also identify signals of negative temporal covariance corresponding to reversals in the direction of selection for a reasonable proportion of loci over the time course of a selection experiment. Overall, we find that in the three studies we analyzed, linked selection has a large impact on short-term allele frequency dynamics that is readily distinguishable from genetic drift.

Impact of white-spotting alleles, including W20, on phenotype in the American Paint Horse.

The American Paint Horse Association (APHA) records pedigree and performance information for their breed, a stock-type horse valued as a working farm or ranch horse and as a pleasure horse. As the name implies, the breed is also valued for its attractive white-spotting patterns on the coat. The APHA utilizes visual inspections of photographs to determine if coat spotting exceeds threshold anatomical landmarks considered characteristic of desirable patterns. Horses with sufficient white patterning enter the 'Regular' registry, rather than the 'Solid Paint-Bred' division, providing a threshold modeled phenotype. Genetic studies previously defined sequence variants corresponding to 35 alleles for white spotting in the horse. Here, we calculate the allele frequencies for nine common white-spotting alleles in the American Paint Horse using a sample of 1054 registered animals. The APHA spotting phenotype is altered by additive interactions among spotting loci, and epistatically by the MC1R and ASIP genes controlling pigment production. The W20 allele within the KIT gene, independent of other known spotting alleles, was strongly associated with the APHA-defined white-spotting phenotype (P = 1.86 × 10-18 ), refuting reports that W20 acts only as a modifier of other underlying white-spotting patterns. The parentage of an individual horse, either American Paint or American Quarter Horse, did not alter the likelihood of its entering the APHA Regular Registry. An empirical definition of the action of these genetic loci on the APHA-defined white-spotting phenotype will allow more accurate application of genome-assisted selection for improving color production and the marketability of APHA horses.

Role of GJB2 and GJB6 in Iranian Nonsyndromic Hearing Impairment: From Molecular Analysis to Literature Reviews.

Background: Hearing impairment (HI) is a heterogeneous disorder. GJB2 and GJB6 genes are typically the first line of genetic screening before proceeding to any massive parallel sequencing. We evaluated the clinical utility of GJB2 and GJB6 testing in the Iranian population. Methods: GJB2 and GJB6 were sequenced. PubMed and Google Scholar were searched for Iranian publications on deletions in the DFNB1 locus. Results: We detected mutations of GJB2 in 16.5%, and no mutations of GJB6. Literature review revealed no reports of mutations of GJB6 in the Iranian population. Conclusion: This data and literature reviews indicate that GJB6 is not commonly responsible for Iranian nonsyndromic HI. Hence, the clinical utility of GJB6 genetic analysis as a first line for HI evaluation does not have the same utility as GJB2. The study is consistent with recent studies emphasizing the role of ethnicity in the selection of HI genetic testing strategy.

HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype.

The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

On the interpretation and relevance of the Fundamental Theorem of Natural Selection.

The attempt to understand the statement, and then to find the interpretation, of Fisher's "Fundamental Theorem of Natural Selection" caused problems for generations of population geneticists. Price's (1972) paper was the first to lead to an understanding of the statement of the theorem. The theorem shows (in the discrete-time case) that the so-called "partial change" in mean fitness of a population between a parental generation and an offspring generation is the parental generation additive genetic variance in fitness divided by the parental generation mean fitness. In the continuous-time case the partial rate of change in mean fitness is equal to the parental generation additive genetic variance in fitness with no division by the mean fitness. This "partial change" has been interpreted by some as the change in mean fitness due to changes in gene frequency, and by others as the change in mean fitness due to natural selection. (Fisher variously used both interpretations.) In this paper we discuss these interpretations of the theorem. We indicate why we are unhappy with both. We also discuss the long-term relevance of the Fundamental Theorem of Natural Selection, again reaching a negative assessment. We introduce and discuss the concept of genic evolutionary potential. We finally review an optimizing theorem that involves changes in gene frequency, the additive genetic variance in fitness and the mean fitness itself, all of which are involved in the Fundamental Theorem of Natural Selection, and which is free of the difficulties in interpretation of the Fundamental Theorem of Natural Selection.

Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women.

PURPOSE: It is important to identify a 'metabolically unhealthy obese' subset with higher cardiovascular risk among obese individuals. We investigated the associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors among Korean obese women. METHODS: This study was a sub-investigation of a double-blind randomized controlled trial that examined the additive effect of or list at on weight loss with sibutramine. A sample of 111 obese women were divided into T-carriers (CT/TT) or a homozygous CC group, according to the presence of the 825T allele at GNB3. These groups were compared to determine their associations with obesity-related metabolic risk factors, i.e., fasting plasma glucose, serum lipids, serum insulin/insulin resistance, and abdominal fat amounts. RESULTS: The allele frequencies of the GNB3 polymorphism were C allele = 59.5% and T allele = 40.5%. The T allele was found to be significantly associated with greater visceral fat and higher serum lipids, and these significances remained robust after adjusting for potential covariates. CONCLUSIONS: The GNB3 825T polymorphism is significantly associated with greater visceral fat and higher serum lipids in Korean obese women and it suggests that the GNB3 C825T is a determinant of obesity-related metabolic traits in this population.

Association of SOD2, GPX1, CAT, and TNF genetic polymorphisms with oxidative stress, neurochemistry, psychopathology, and extrapyramidal symptoms in schizophrenia.

There is a growing body of evidence confirming the involvement of oxidative stress and inflammation in pathogenesis of schizophrenia. Inter-individual variation in antioxidant capacity caused by different genetic profile could potentially influence patient's susceptibility to oxidative damage. In this study we evaluated the polymorphisms of manganese superoxide dismutase SOD2Val16Ala, glutathione peroxidase GPX1Pro200Leu, catalase CAT-262C>T and CATc.66+78C>T, and tumour necrosis factor-alpha TNF-308G>A by assessing their association with biomarkers of oxidative stress, neurochemistry, psychopathology of schizophrenia and extrapyramidal symptoms in Caucasian schizophrenia patients treated with haloperidol depot. TNF-308G>A was associated with the increased risk of parkinsonism. No major role of polymorphism of SOD2Val16Ala, CAT-262C>T nor GPX1Pro200Leu in psychopathology of schizophrenia or extrapyramidal symptoms was observed. SOD2Val16Ala polymorphism was associated with dopamine plasma concentration and blood concentration ratio between reduced and oxidised form of glutathione, while GPX1Pro200Leu was related with concentration of reduced glutathione. CATc.66+78C>T was associated with noradrenaline plasma concentration and PANSS negative score. PANSS positive and general scores, were associated with the increased risk of tardive dyskinesia. PANSS positive, negative, and general scores, and GAF score were all associated with the increased risk of akathisia.

Association study between FSHR Ala307Thr and Ser680Asn variants and polycystic ovary syndrome (PCOS) in Northern Chinese Han women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common complex genetic endocrinopathy. It has high heritability, and twin studies indicate that it is a complex polygenic disorder. Searching for major genes of PCOS is crucial to clarify its molecular pathogenesis. A previous genome-wide association study in Chinese women with PCOS identified a region on chromosome 2p16.3 that encodes the follicle-stimulating hormone receptor (FSHR) genes as a reproducible PCOS susceptibility locus. In the present study, we performed a replication analysis of the association between two common variants of the FSHR gene and PCOS in Northern Chinese Han women. RESULTS: We recruited 384 unrelated PCOS patients and 768 healthy individuals from the Shaanxi province in the northern part of China. Two polymorphisms (Ala307Thr and Ser680Asn) of the FSHR gene and the clinical characteristics of the study subjects were analyzed in the case-control sample. The frequency of FSHR Ala307Thr and Ser680Asn variants along with the haplotype was not significantly different between the PCOS patients and the controls; however, the Ser680 variants may be associated with high levels of FSH and low E2 levels. CONCLUSION: The variant of Ser680 was not associated with PCOS but it may be related to high FSH levels. The present study suggests that the two variants of the FSHR gene are not a causative factor of PCOS in Northern Chinese Han women.

Impact of polymorphisms of the genes encoding angiotensin II-forming enzymes on the progression of IgA nephropathy.

BACKGROUND/AIMS: Angiotensin II has been shown to play an important role in various renal diseases. Genetic polymorphisms of the renin-angiotensin system have been reported to be related to the clinical outcomes in immunoglobulin A nephropathy (IgAN). We investigated the association of polymorphisms of the genes encoding major angiotensin II-forming enzymes with the development and progression of IgAN among Korean patients. METHODS: A total of 261 IgAN patients and 300 healthy controls were studied. The polymorphisms of angiotensin-converting enzyme gene (I/D, A2350G) and chymase (CMA) gene (rs1800875, rs1800876) were determined. RESULTS: No significant difference was observed in the genotype and allele frequencies of the polymorphisms between IgAN patients and controls. The frequency of AA/AG genotypes of CMA rs1800875 and CC/CT genotype of CMA rs1800876 were significantly higher in patients with progressive disease course than in those with stable course (53.2 vs. 38.6%, p = 0.029; 89.6 vs. 78.3%, p = 0.031, respectively). In the Cox regression model with adjustment for clinical risk factors, CMA rs1800875 AA/AG genotypes remained an independent risk factor (hazard ratio 2.351; p = 0.001). CONCLUSION: Our results suggest that the CMA rs1800875 polymorphism is associated with the progression of IgAN in Korean patients.

Bistability in two-locus models with selection, mutation, and recombination.

The evolutionary effect of recombination depends crucially on the epistatic interactions between linked loci. A paradigmatic case where recombination is known to be strongly disadvantageous is a two-locus fitness landscape displaying reciprocal sign epistasis with two fitness peaks of unequal height. Although this type of model has been studied since the 1960s, a full analytic understanding of the stationary states of mutation-selection balance was not achieved so far. Focusing on the bistability arising due to the recombination, we consider here the deterministic, haploid two-locus model with reversible mutations, selection and recombination. We find analytic formulae for the critical recombination probability r ( c ) above which two stable stationary solutions appear which are localized on each of the two fitness peaks. We also derive the stationary genotype frequencies in various parameter regimes. In particular, when the recombination rate is close to r ( c ) and the fitness difference between the two peaks is small, we obtain a compact description in terms of a cubic polynomial which is analogous to the Landau theory of physical phase transitions.

Possible genetic sign of heat stress adaptation in Hungarian Grey Bos taurus breed.

The synthesis of Heat Shock Protein 70.2 mRNA is also regulated by the Upper Promoter elements of the gene. This promoter region is polymorphic in cattle. These polymorphisms have a major effect on the activity of the mRNA transcription. In a comparison of quantity of transcribed mRNA from the wild type and AP2 mutant allele the wild type can produce 2-3-fold more transcripts.The Hungarian Grey Cattle (HG) and Norwegian Red (NFR) as control breed were genotyped with PCR-RFLP method. Our results showed that the frequencies of alleles in breeds (p(wt)HG = 0.859419, p(wt)NFR = 0.5) are different. The effective response to heat stress in the Norwegian Red seems to be less important than in the Hungarian Grey breed. The extensive keeping in hot and arid region during centuries could have been proved as selection pressure for the heat tolerance.Our results combined with the global climate forecasts emphasize the role of autochthonous, well adopted, heat tolerant breeds in the near future.

[The Dagestan gene pool: polymorphism of immunogenetic and biochemical markers in Kumyks].

This study is a part of long-term investigations devoted to the analysis of the gene pool of Dagestan ethnic groups. The phenotype (in %), gene, and haplotype frequencies in Kumyk ethnic group are reported. A total of 39 alleles and six haplotypes of 14 loci (AB0, Rhesus, P, Levis, Kell, HP, GC, C'3, TF, 6PGD, GLO1, ESD, ACP, and PGM1) of immunobiochemical genetic marker systems were examined. Rare haplotypes of the Rhesus system were identified, including CDE in the Karabudakhkent population with the frequency of 0.030, and Cde and cdE in the Dorgeli population with the frequencies of 0.034 and 0.38, respectively. Similarly to the other ethnic populations of Dagestan examined, Kukyk populations carried rare, albeit typically "Caucasoid" gene ACP1(c) of the AcP1 locus. The frequency of this allele in the two populations was similar, constituting 0.031 for Karabudakhkent and 0.032 for Dorgeli. In Kumyks, allele frequencies of the AB0, Rhesus, P, Lewis, Kell, HP, GC, C'3, TF, 6PGD, GLO1, ESD, ACP, but not PGM1, systems were similar to the mean allele frequencies at these loci observed in the other ethnic groups from the Dagestan, Caucasus, and the whole European historical ethnographic province. At the same time, the allele frequency values obtained were different from those for the populations of Kazakhstan, Central Asia, Siberia, and the Ruswsian Far East. Thus, the results obtained for classical genetic markers indicate that Kumyks are genetically closer to the indigenous populations of Dagestan than to Turkic-speaking populations. Analysis of the fit of the observed phenotype frequencies to the Hardy-Weinberg expectations showed that compared to other indigenous populations of Dagestan examined, in Kumyks the genetic state of the population upon random allele association was close to equilibrium. Probably, this state was determined by practical absence of the consanguineous marriages upon preservation of intra-aul endogamy.

[The microsatellite polymorphism and gene flow in the contact zone of four common shrew (Sorex araneus L., Mammalia) chromosome races].

The variation of microsatellite loci in 130 individuals of four common shrew chromosome races (Moscow, Western Dvina, Seliger, and St. Petersburg) contacting on the Valdai Hills was studied. A low level of genetic differences between the chromosome races, which differ at three-five fixed diagnostic metacentric chromosomes, was found. The genetic differentiation within the races is more considerable as compared with that between the races. A high deficiency in heterozygotes was recorded; presumably, this is connected with regular variation in the population sizes. It is assumed that the fixation of centric chromosome fusions was supported by selection (drive) in the evolution of the common shrew against the background of a neutral evolution of the microsatellite loci.

Patterns of allele frequency differences among domestic cat breeds assessed by a 63K SNP array.

Cats are ubiquitous companion animals that have been keenly associated with humans for thousands of years and only recently have been intentionally bred for aesthetically appealing coat looks and body forms. The intense selection on single gene phenotypes and the various breeding histories of cat breeds have left different marks on the genomes. Using a previously published 63K Feline SNP array dataset of twenty-six cat breeds, this study utilized a genetic differentiation-based method (di) to empirically identify candidate regions under selection. Defined as three or more overlapping (500Kb) windows of high levels of population differentiation, we identified a total of 205 candidate regions under selection across cat breeds with an average of 6 candidate regions per breed and an average size of 1.5 Mb per candidate region. Using the combined size of candidate regions of each breed, we conservatively estimate that a minimum of ~ 0.1-0.7% of the autosomal genome is potentially under selection in cats. As positive controls and tests of our methodology, we explored the candidate regions of known breed-defining genes (e.g., FGF5 for longhaired breeds) and we were able to detect the genes within candidate regions, each in its corresponding breed. For breed specific exploration of candidate regions under selection, eleven representative candidate regions were found to encompass potential candidate genes for several phenotypes such as brachycephaly of Persian (DLX6, DLX5, DLX2), curled ears of American Curl (MCRIP2, PBX1), and body-form of Siamese and Oriental (ADGRD1), which encourages further molecular investigations. The current assessment of the candidate regions under selection is empiric and detailed analyses are needed to rigorously disentangle effects of demography and population structure from artificial selection.

A variant near the interleukin-6 gene is associated with fat mass in Caucasian men.

CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.

Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death.

Caspase-independent death mechanisms have been shown to execute apoptosis in many types of neuronal injury. P53 has been identified as a key regulator of neuronal cell death after acute injury such as DNA damage, ischemia, and excitotoxicity. Here, we demonstrate that p53 can induce neuronal cell death via a caspase-mediated process activated by apoptotic activating factor-1 (Apaf1) and via a delayed onset caspase-independent mechanism. In contrast to wild-type cells, Apaf1-deficient neurons exhibit delayed DNA fragmentation and only peripheral chromatin condensation. More importantly, we demonstrate that apoptosis-inducing factor (AIF) is an important factor involved in the regulation of this caspase-independent neuronal cell death. Immunofluorescence studies demonstrate that AIF is released from the mitochondria by a mechanism distinct from that of cytochrome-c in neurons undergoing p53-mediated cell death. The Bcl-2 family regulates this release of AIF and subsequent caspase-independent cell death. In addition, we show that enforced expression of AIF can induce neuronal cell death in a Bax- and caspase-independent manner. Microinjection of neutralizing antibodies against AIF significantly decreased injury-induced neuronal cell death in Apaf1-deficient neurons, indicating its importance in caspase-independent apoptosis. Taken together, our results suggest that AIF may be an important therapeutic target for the treatment of neuronal injury.

The T9861C Mutation in the mtDNA-Encoded Cytochrome C Oxidase Subunit III Gene Occurs in High Frequency but with Unequal Distribution in the Alzheimer's Disease Brain.

Mitochondrial dysfunction is recognized as a critical component in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Deficits in oxidative capacity and, specifically, cytochrome c oxidase (CO) activity have been reported in AD brains and platelets. We previously identified a point mutation at np 9861 in AD brain mitochondrial DNA (mtDNA) that alters amino acid 219 of subunit III of CO from phenylalanine to leucine. We rapidly screened and quantitated levels of T9861C in samples using mismatched PCR-RFLP and nucleotide extension assays. Six of 40 AD brains possessed the T9861C mutation (designated AD+) compared to zero of 40 age-matched control brains. The 15% frequency of T9861C in AD brain is 115-fold higher than the frequency (0.13%) reported in 9,986 human mtDNA samples queried in world-wide databases. T9861C is heteroplasmic, with mutant load varying from 11% to >95%. Detected initially in parietal cortex, T9861C is not localized to that region but is also found in temporal cortex and caudate but not in hippocampus. The mutant load is unequally distributed throughout these brain regions with the highest load occurring in the parietal or temporal cortex. CO activity normalized to citrate synthase (CS) is reduced an average of 48.5% in AD+ brains. CO/CS ratios amongst controls and the two AD populations (AD and AD+) were significantly different (p = 0.001). Post hoc differences were also significant between controls and AD+ (p = 0.001) and controls and AD (p = 0.019). There was no significant difference between AD and AD+ (p = 0.317).

Effect of selective fatiguing of the shank muscles on single-leg-standing sway.

Control of standing requires the continuous activity of the leg muscles. In single leg standing the system is less redundant and muscular activity is more intensive. The objective of this study was to examine the effect of force imbalance of the shank muscles, evoked by their selective fatiguing, on postural control in single-leg standing. Five healthy subjects performed two single-leg standing trials, lasting as long as the subject could maintain steady balance, and separated by a 240s quasi-isotonic sustained effort to induce fatigue of the Tibialis Anterior and Peroneus muscles. The following were on-line monitored: sway-related parameters, e.g., ground reaction force and center of pressure in the standing trials; and electromyogram of the Tibialis Anterior, Peroneus and Gastrocnemius muscles in all experiments. Simple and multiple linear regressions served to study the fatigue effects on the relationship between muscle activity and postural sway. The results indicate that the evoked muscle imbalance leads to (a) increased postural sway; (b) increased correlation between muscle activity, and sway-related parameters. Thus, with the reduction of the level of redundancy the system becomes more synchronized. These results have potential relevance for cases of muscle impairment, in which electrical stimulation is required to augment muscle activity.

[Distribution of two chromosome races of the common shrew (Sorex araneus L.) in the hybrid zone: may a change of the dispersal mode maintain independent gene frequencies?].

Combination of different dispersal modes may itself, without external obstacles, lead to the appearance of subdivided populations and maintain the existence of independent population systems. The common shrew, a mammal convenient for studying different levels of intraspecific differentiation, was the object of the study. Empirical data have been used for simulation taking into account the change of dispersal modes in the population area. The obtained results agree with empirical data on the distribution of races and hybrids in the hybrid zone of chromosome races Moscow and Seliger. Change of the dispersal mode may maintain independent population dynamics and, in the case of chromosome races, prevent the migration of parental individuals into the territory of the other race.

[New data on the distribution of hybrid necrosis genes in winter bread wheat (Triticum aestivum L.) cultivars].

Hybrid necrosis genotypes have been identified in 125 Russian cultivars of winter bread wheat. More than half of them (56%) carry the Ne2 gene (genotype ne1ne1Ne2Ne2); others are free of necrosis genes (genotype ne1ne1ne2ne2). The possible causes of the increase in the Ne2 allele frequency and the loss of the Ne1Ne1ne2ne2 genotype in modem Russian cultivars of winter wheat are discussed. The principal component method has been used to compare the structures of the genetic diversity of cultivars differing in the hybrid necrosis genotype. It has been found that the Ne2 allele in winter wheat cultivars from northern Russia has originated from the cultivar Mironovskaya 808, whereas the cultivar Bezostaya 1 is not a source of this gene. In cultivars from southern Russia, the presence of the Ne2 allele is also mainly accounted for by the use of Mironovskaya 808 wheat in their breeding. The recessive genotype is explained by the presence of descendants of the cultivar Odesskaya 16 in the pedigrees of southern Russian winter wheats. The genetic relationship of cultivars with identical and different necrosis genotypes has been analyzed in nine regions of the Russian Federation.