Distorted Segregation Ratios Research Articles

Transmission ratio distortion detection by neutral genetic markers in the Pura Raza Española horse breed

Transmission Ratio Distortion (TRD) is a genetic phenomenon widely demonstrated in several livestock species, but barely in equine species. The TRD occurs when certain genotypes are over- or under-represented in the offspring of a particular mating and can be caused by a variety of factors during gamete formation or during embryonic development. For this study, 126 394 trios consisting of a stallion, mare, and offspring were genotyped using a panel of 17 neutral microsatellite markers recommended by the International Society for Animal Genetics for paternity tests and individual identification. The number of alleles available for each marker ranges from 13 to 18, been 268 the total number of alleles investigated. The TRDscan v.2.0 software was used with the biallelic procedure to identify regions with distorted segregation ratios. After completing the analysis, a total of 12 alleles (out of 11 microsatellites) were identified with decisive evidence for genotypic TRD; 3 and 9 with additive and heterosis patterns, respectively. In addition, 19 alleles (out of 10 microsatellites) were identified displaying allelic TRD. Among them, 14 and 5 were parent-unspecific and stallion-mare-specific TRD. Out of the TRD regions, 24 genes were identified and annotated, predominantly associated with cholesterol metabolism and homeostasis. These genes are often linked to non-specific symptoms like impaired fertility, stunted growth, and compromised overall health. The results suggest a significant impact on the inheritance of certain genetic traits in horses. Further analysis and validation are needed to better understand the TRD impact before the potential implementation in the horse breeding programme strategies.

Inheritance of Unilateral Incompatibility in the Genus Capsicum

Unilateral incompatibility is reported to occur between the species of Capsicum pubescens complex (Capsicum cardenasii Capsicum. eximium and Capsicum pubescens) and other species of genus Capsicum when the latter are used as the male parent. The relationship between self-incompatibility and unilateral incompatibility are yet to be resolved even in the most intensively investigated crosses within and between species of Lycopersicon and Solanum. Unilateral incompatibility in Capsicum has been less intensively studied compared to some other genus in family Solanaceae. This study was, therefore, conducted to help us to understand the genetic control of unilateral incompatibility in Capsicum. Experiment results showed that while the pistil behaviour of F1 hybrids agrees with the pistil behaviour of F1 hybrids from unilaterally incompatible crosses in other genera of Solanaceae, the pollen behaviour does not agree with data obtained from other genera of Solanaceae. No segregation ratio was obtained for unilateral incompatibility in the backcross progenies, this result does not agree with data from other genera in the Solanaceae either. Possible reasons for not obtaining segregation for unilateral incompatibility may be the small size of backcross progenies and/or distorted segregation ratios. As a conclusion it seemed more probable that, in Capsicum, unilateral incompatibility has arisen as a by-product of genetic divergence between the C. pubescens complex and the other chile peppers, not as a product of natural selection.

Introgressing cry1Ac for Pod Borer Resistance in Chickpea Through Marker-Assisted Backcross Breeding.

The gram pod borer Helicoverpa armigera is a major constraint to chickpea (Cicer arietinum L.) production worldwide, reducing crop yield by up to 90%. The constraint is difficult to overcome as chickpea germplasm including wild species either lacks pod borer resistance or if possessing resistance is cross-incompatible. This study describes conversion of elite but pod borer-susceptible commercial chickpea cultivars into resistant cultivars through introgression of cry1Ac using marker-assisted backcross breeding. The chickpea cultivars (PBG7 and L552) were crossed with pod borer-resistant transgenic lines (BS 100B and BS 100E) carrying cry1Ac that led to the development of BC1F1, BC1F2, BC1F3, BC2F1, BC2F2, and BC2F3 populations from three cross combinations. The foreground selection revealed that 35.38% BC1F1 and 8.4% BC1F2 plants obtained from Cross A (PBG7 × BS 100B), 50% BC1F1 and 76.5% BC1F2 plants from Cross B (L552 × BS 100E), and 12.05% BC2F2 and 82.81% (average) BC2F3 plants derived from Cross C (PBG7 × BS 100E) carried the cry1Ac gene. The bioassay of backcross populations for toxicity to H. armigera displayed up to 100% larval mortality. BC1F1 and BC1F2 populations derived from Cross B and BC2F3 population from Cross C segregated in the Mendelian ratio for cry1Ac confirmed inheritance of a single copy of transgene, whereas BC1F1 and BC1F2 populations obtained from Cross A and BC2F2 population from Cross C exhibited distorted segregation ratios. BC1F1 plants of Cross A and Cross B accumulated Cry1Ac protein ranging from 11.03 to 11.71 µgg−1 in leaf tissue. Cry1Ac-positive BC2F2 plants from Cross C demonstrated high recurrent parent genome recovery (91.3%) through background selection using SSR markers and phenome recovery of 90.94%, amongst these 30% plants, were homozygous for transgene. The performance of BC2F3 progenies derived from homozygous plants was similar to that of the recurrent parent for main agronomic traits, such as number of pods and seed yield per plant. These progenies are a valuable source for H. armigera resistance in chickpea breeding programs.

Production of doubled-haploid(DH) selfed-progenies in ‘Banpeiyu’ pummelo [Citrus maxima (Burm.) Merr.] and its genetic analysis with simple sequence repeat markers

The genetic analysis of five haploid plants (BX1-BX5) of ‘Banpeiyu’ pummelo (BP), [Citrus maxima (Burm.) Merr.] using 32 simple sequence repeat (SSR) markers carried out for the purpose of confirming their gynogenetic origin and genetic differences. As the results, all the haploid plants possessed only either one of the BP alleles, confirming that they are gynogenetic origin. We also confirmed that BX1 and its doubled haploid (BX1-DH) have exactly the same SSR alleles. Interestingly, all the five haploids had common alleles on the linkage group (LG) 6 in the case of three markers. Then, we performed self-pollination of DH plants and reciprocal crosses between DH and BP, which has strong self-incompatibility. The seeds obtained by these crosses germinated in vitro or ex vitro normally and developed into diploid seedlings, except for one tetraploid seedling. Genetic analysis of these seedlings with 32 SSR markers revealed that segregation ratios of the 32 loci in the 30 BP inbred, 30 BP x DH and 30 DH x BP progenies mostly fitted to the expected ratios. However, significantly distorted segregation ratios were found in one, five and three SSR markers for BP inbred, BP x DH and DH x BP progenies, respectively. All of the 30 DH inbred progenies showed exactly the same SSR alleles as the original DH. This is the first example in which self and back cross progenies of DH in fruit crops were genetically analyzed using SSR markers.

QTL Mapping and Inheritance of Clubroot Resistance Genes Derived From Brassica rapa subsp. rapifera (ECD 02) Reveals Resistance Loci and Distorted Segregation Ratios in Two F2 Populations of Different Crosses

In this study, Brassica rapa subsp. rapifera (ECD 02) which exhibits broad-spectrum resistance to many Canadian Plasmodiophora brassicae isolates was crossed with two clubroot-susceptible B. rapa accessions to produce two F2 populations. The F2 plants were screened against P. brassicae pathotypes 3H, 5X, and 5G. The Chi-square goodness of fit test showed that the vast majority (≈75%) of the crosses that produced the F2 populations showed segregation ratios of 9R:7S, 7R:9S, 13R:3S, 3R:13S, 5R:11S, 11R:5S, and 1R:15S. These were modifications of the 15R:1S ratio expected for the inheritance of two dominant major clubroot resistance (CR) genes from ECD 02. The distorted segregation ratios suggest that the two resistance genes are on different chromosomes and that two genes interact in an epistatic manner to confer resistance. Genotyping was conducted with 144 PCR-based markers in the two F2 populations. Linkage and QTL analysis with the polymorphic markers identified two QTLs on chromosome A03 to be associated with resistance to P. brassicae pathotypes 5X and 5G in Popl#1 while only the second QTL on chromosome A03 was associated with resistance to pathotypes 5X and 5G in Popl#2. The QTLs clustered in genomic regions on the A03 chromosome of B. rapa where the CRa/CRbKato gene(s) are mapped. In addition, the Crr1 gene on the A08 chromosome of B. rapa was detected in the two F2 populations. Therefore, the phenotypic and molecular data confirm the existence of two CR genes in ECD 02. This is the first study that shows that major dominant genes in Brassica interact in a non-additive manner to confer resistance to different P. brassicae pathotypes.Key Message: This study provides knowledge on the inheritance and type of gene action for clubroot resistance derived from Brassica rapa subsp. rapifera (ECD 02). The results indicated that duplicate recessive and recessive suppression epistatic interactions, digenic additivity and complementary gene action between the CRa/CRbKato gene(s) on the A03 and the Crr1 gene on the A08 chromosome of B. rapa controlled clubroot resistance to P. brassicae pathotypes 3H, 5X and 5G.

Effects of ion beam irradiation on size of mutant sector and genetic damage in Arabidopsis

Size of mutant sector and genetic damage were evaluated in Arabidopsis to further our understanding of effective ion beam use in plant mutation breeding. Arabidopsis seeds, heterozygous for the GLABRA1 (GL1) gene (GL1/gl1-1), were irradiated with 15.8MeV/u neon ions (mean linear energy transfer (LET): 352keV/μm), 17.3MeV/u carbon ions (113keV/μm), or 60Co gamma rays. The frequency and size of glabrous sectors generated because of inactivation of the GL1 allele were examined. The frequency and overall size of large deletions were evaluated based on the loss of heterozygosity of DNA markers using DNA isolated from glabrous tissue. Irrespective of the radiation properties, plants with mutant sectors were obtained at similar frequencies at the same effective dosage necessary for survival reduction. Ion beams tended to induce larger mutant sectors than gamma rays. The frequency of large deletions (>several kbp) increased as the LET value increased, with chromosome regions larger than 100kbp lost in most large deletions. The distorted segregation ratio of glabrous plants in the progenies of irradiated GL1/gl1-1 plants suggested frequent occurrence of chromosome rearrangement, especially those subjected to neon ions. Exposure to ion beams with moderate LET values (30–110keV/μm) is thought effective for inducing mutant sectors without causing extensive genetic damage.

Disomic Inheritance and Segregation Distortion of SSR Markers in Two Populations of Cynodon dactylon (L.) Pers. var. dactylon.

Common bermudagrass [C. dactylon (L.) Pers. var. dactylon] is economically and environmentally the most important member among Cynodon species because of its extensive use for turf, forage and soil erosion control in the world. However, information regarding the inheritance within the taxon is limited. Accordingly, the objective of this study was to determine qualitative inheritance mode in common bermudagrass. Two tetraploid (2n = 4x = 36), first-generation selfed (S1) populations, 228 progenies of ‘Zebra’ and 273 from A12359, were analyzed for segregation with 21 and 12 simple sequence repeat (SSR) markers, respectively. It is concluded that the inheritance mode of tetraploid bermudagrass was complete or near complete disomic. It is evident that the two bermudagrass parents had an allotetraploid genome with two distinct subgenomes since 33 SSR primer pairs amplified 34 loci, each having two alleles. Severe transmission ratio distortions occurred in the Zebra population while less so in the A12359 population. The findings of disomic inheritance and segregation ratio distortion in common bermudagrass is significant in subsequent linkage map construction, quantitative trait locus mapping and marker-assisted selection in the species.

Analysis of gene-disruption mutants of a sucrose phosphate synthase gene in rice, OsSPS1, shows the importance of sucrose synthesis in pollen germination

The molecular function of an isoform of sucrose phosphate synthase (SPS) in rice, OsSPS1, was investigated using gene-disruption mutant lines generated by retrotransposon insertion. The progeny of the heterozygote of disrupted OsSPS1 (SPS1+/−) segregated into SPS1+/+, SPS1+/−, and SPS1−/− at a ratio of 1:1:0. This distorted segregation ratio, together with the expression of OsSPS1 in the developing pollen revealed by quantitative RT-PCR analysis and promoter–beta-glucuronidase (GUS) fusion assay, suggested that the disruption of OsSPS1 results in sterile pollen. This hypothesis was reinforced by reciprocal crosses of SPS1+/− plants with wild-type plants in which the disrupted OsSPS1 was not paternally transmitted to the progeny. While the pollen grains of SPS+/− plants normally accumulated starch during their development, pollen germination on the artificial media was reduced to half of that observed in the wild-type control. Overall, our data suggests that sucrose synthesis via OsSPS1 is essential in pollen germination in rice.

Segregation distortion caused by weak hybrid necrosis in recombinant inbred lines of common wheat

Segregation distortion of molecular markers is closely related to hybrid incompatibility in progeny from intraspecific crosses. Recent reports in higher plants have demonstrated that hybrid sterility results in segregation distortion at the causal gene regions in progeny of intraspecific crosses. Ne1 and Ne2 complementary loci are known to control hybrid necrosis in intraspecific crosses of common wheat cultivars. Here, we examine the effect of a weak necrosis allele Ne1(w) on the segregation ratio of molecular markers in recombinant inbred lines (RILs) of common wheat. Some RILs showed accelerated cell death in the leaves at the heading stage due to the epistatic interaction between two quantitative trait loci (QTL) on chromosomes 5B and 2B. Chromosomal localization of these QTL corresponding to Ne1(w) and Ne2 showed distorted segregation ratios of assigned markers having oppositely biased direction. Although the Ne1(w) and Ne2 interaction had no obvious effect on seed fertility, Ne1(w) reduced completion of grain development under the Ne2-homozygous background. This reduction might be one of causes that induces segregation distortion in the 5B and 2B chromosomal regions of RILs. The present study demonstrated that weak hybrid necrosis has limited phenotypic effects; it causes segregation distortion in progeny from intraspecific crosses.

Involvement of MLPK Pathway in Intraspecies Unilateral Incompatibility Regulated by a Single Locus With Stigma and Pollen Factors

Plants have evolved many systems to prevent undesirable fertilization. Among these, incompatibility is a well-organized system in which pollen germination or pollen tube growth is inhibited in pistils. We previously found that a novel one-way pollen–stigma incompatibility response [unilateral incompatibility (UI)] occurred between two self-incompatible Brassica rapa plants, a Turkish line, and a Japanese cultivated hybrid variety, “Osome.” Pollen from the Turkish line is rejected on the stigma of the Osome line, but the reverse cross is compatible; such a UI phenotype closely resembles self-incompatibility (SI). The pollen factor of this UI has been genetically explained by a single locus which is different from the S-locus. In this study, we performed further genetic analyses of this intraspecies UI and showed that the stigma factor was also controlled by a single locus, and we named the loci corresponding to the stigma and pollen factors of the intraspecies UI, stigmatic unilateral incompatibility (SUI), and pollen unilateral incompatibility (PUI) loci, respectively. Interestingly, segregation analyses of SUI and PUI indicated that they are closely linked to each other and behave as a single unit. To investigate the effect of an SI-related gene, MLPK in this UI, we produced segregation lines for SUI and mlpk. A distorted segregation ratio of SUI phenotype in an mlpk background indicated involvement of MLPK in SUI, suggesting the existence of an MLPK-dependent novel pollen–stigma recognition mechanism.

Development of highly polymorphic EST-SSR markers and segregation in F1 hybrid population of Vitis vinifera L.

The objectives of this investigation were to develop and validate the expressed sequence tag (EST)-simple sequence repeat (SSR) markers from large EST sequences, and to study the segregation and distribution of SSRs within two grapevine parental lines. In total, 94 F₁ lines crossed between "Early Rose" and "Red Globe" were studied. Approximately 2100 EST-SSR sequences of Vitis vinifera L. were searched for SSRs and analyzed for the design of polymerase chain reaction (PCR) primers amplifying the SSR-rich regions. Trinucleotide repeats were found to be the most abundant, followed by other nucleotide repeats. A total of 182 SSR primer pairs were first developed for the study on the parental polymorphism. Among the 182 SSR primers, 142 primer pairs (78%) could amplify the anticipated PCR products, among which only 52 primer pairs (36.62%) showed polymorphism between the two parents. These polymorphic bands were further surveyed among the 94 F₁ lines, and the results showed that a total of 162 bands were amplified, and 98 of them were polymorphic in both parents (60.86% polymorphism), with an average of 1.88 polymorphic DNA bands for each primer pair. After testing with the chi-square test, 33 of the clearly amplified polymorphic bands followed a 3:1 ratio, and 37 followed a 1:1 ratio. The rest showed distorted segregation ratios.

Integration of Two Diploid Potato Linkage Maps with the Potato Genome Sequence

To facilitate genome-guided breeding in potato, we developed an 8303 Single Nucleotide Polymorphism (SNP) marker array using potato genome and transcriptome resources. To validate the Infinium 8303 Potato Array, we developed linkage maps from two diploid populations (DRH and D84) and compared these maps with the assembled potato genome sequence. Both populations used the doubled monoploid reference genotype DM1-3 516 R44 as the female parent but had different heterozygous diploid male parents (RH89-039-16 and 84SD22). Over 4,400 markers were mapped (1,960 in DRH and 2,454 in D84, 787 in common) resulting in map sizes of 965 (DRH) and 792 (D84) cM, covering 87% (DRH) and 88% (D84) of genome sequence length. Of the mapped markers, 33.5% were in candidate genes selected for the array, 4.5% were markers from existing genetic maps, and 61% were selected based on distribution across the genome. Markers with distorted segregation ratios occurred in blocks in both linkage maps, accounting for 4% (DRH) and 9% (D84) of mapped markers. Markers with distorted segregation ratios were unique to each population with blocks on chromosomes 9 and 12 in DRH and 3, 4, 6 and 8 in D84. Chromosome assignment of markers based on linkage mapping differed from sequence alignment with the Potato Genome Sequencing Consortium (PGSC) pseudomolecules for 1% of the mapped markers with some disconcordant markers attributable to paralogs. In total, 126 (DRH) and 226 (D84) mapped markers were not anchored to the pseudomolecules and provide new scaffold anchoring data to improve the potato genome assembly. The high degree of concordance between the linkage maps and the pseudomolecules demonstrates both the quality of the potato genome sequence and the functionality of the Infinium 8303 Potato Array. The broad genome coverage of the Infinium 8303 Potato Array compared to other marker sets will enable numerous downstream applications.

Characterization of 215 simple sequence repeat markers in creeping bentgrass (Agrostis stolonifera L.)

Creeping bentgrass (Agrostis stolonifera L.) is a versatile, cross-pollinated, temperate and perennial turfgrass species. It occurs naturally in a wide variety of habitats and is also cultivated on golf courses, bowling greens and tennis courts worldwide. Isozymes and amplified fragment length polymorphisms (AFLPs) have been used to determine genetic diversity, and restriction fragment length polymorphisms (RFLPs) and random amplified polymorphic DNA (RAPDs) were used to construct a genetic linkage map of this species. In the current report, we developed and characterized 215 unique genomic simple sequence repeat (SSR) markers in creeping bentgrass. The SSRs reported here are the first available markers in creeping bentgrass to date. Eight hundred and eighteen alleles were amplified by 215 SSR loci, an average of 3.72 alleles per locus. Fifty-nine per cent of those alleles segregated in a 1:1 Mendelian fashion (P > 0.05). Twenty-two per cent had a distorted segregation ratio (P ≤ 0.05). These SSR markers will be useful for assessing genetic diversity in creeping bentgrass and will be important for the development of genetic linkage maps and identifying quantitative trait loci. These markers could enhance breeding programmes by improving the efficiency of selection techniques.

Female gametophytic mutants of Arabidopsis thaliana identified in a gene trap insertional mutagenesis screen

In plants, the male and female gametophytes represent the haploid generation that alternates with the diploid sporophytic generation. Male and female gametophytes develop from haploid micro- and megaspores, respectively. In flowering plants (angiosperms), the spores themselves arise from the sporophyte through meiotic divisions of sporogenous cells in the reproductive organs of the flower. Male and female gametophytes contain two pairs of gametes that participate in double fertilization, a distinctive feature of angiosperms. In this paper, we describe the employment of a transposon-based gene trap system to identify mutations affecting the gametophytic phase of the plant life cycle. Mutants affecting female gametogenesis were identified in a two-step screen for (i) reduced fertility (seed abortion or undeveloped ovules) and (ii) segregation ratio distortion. Non-functional female gametophytes do not initiate seed development, leading to semi-sterility such that causal or linked alleles are transmitted at reduced frequency to the progeny (non-Mendelian segregation). From a population of 2,511 transposants, we identified 54 lines with reduced seed set (2%). Examination of their distorted segregation ratios and seed phenotypes led to the isolation of 12 gametophytic mutants, six of which are described herein. Chromosomal sequences flanking the transposon insertions were identified and physically mapped onto the genome sequence of Arabidopsis thaliana. Surprisingly, the insertion sites were often associated with chromosomal rearrangements, making it difficult to assign the mutant phenotypes to a specific gene. The mutants were classified according to the process affected at the time of arrest, i.e. showing mitotic, karyogamic, maternal or degenerative phenotypes.

Identification of SSR Markers for Salt-tolerance in Rice Variety CSR10 by Selective Genotyping

A population of 171 F3 genotypes derived from a cross between CSR10 (salt tolerant, indica) and Taraori Basmati (HBC19) was evaluated for various salt-tolerance attributes at vegetative stage using a hydroponic culture system. Substantial variation was observed in F3 population for relative growth rate (range 0.065–0.187), Na-K ratio (0.023–0.376) and visual injury symptoms (score 1–9). The mean individual score of CSR10 × HBC19 F3 plants ranged from 1.7 to 9.0 with mean value of 5.07. Seven of the F3 plants showed transgressive segregation for salt tolerance. F3 individuals at both extremes of the response distribution were selected and genotyped using 30 SSR markers displaying polymorphism between the two parental genotypes. As many as 18/30 SSR markers showed distorted segregation ratios among the 30 selected salt-tolerant and salt-sensitive CSR10 × HBC19 F3 plants. Linear regression analysis showed significant association of three markers (RM162 mapped on chromosome 6, and RM209 and RM287 on chromosome 11) with relative growth rate and two markers (RM212 on chromosome 1 and RM206 on chromosome 11) with Na-K ratio explaining 31.3% and 25.6% of phenotypic variation, respectively.

Analysis of segregation patterns in Machado–Joseph disease pedigrees

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is considered the most common form of SCA worldwide. The main goal of this study was to investigate the presence of segregation ratio distortion (SRD) during transmissions of ATXN3 alleles by MJD patients, evaluating the putative role of SRD in the epidemiological representation of the disease. Sixty-two complete sibships, each with one clinically affected parent, totalling 330 transmissions were selected according to defined criteria and used for segregation analysis. Onset data from MJD patients with Azorean origin was used for residual risk estimates according to different ages. Residual risk values were applied to unaffected offspring to calculate the probability of inheriting the expanded allele. The proportion of offspring that received the expanded or the normal allele from the affected parent was calculated to determine the presence of SRD during transmissions of ATXN3 alleles by MJD patients. Segregation of ATXN3 alleles was in accordance with the expected Mendelian proportions (chi (2) = 0.982, P = 0.322). However, there was a tendency favouring the transmission of the normal alleles. Thus, SRD is not a potential mechanism on the basis of MJD epidemiological representation.

Genetic Analysis of Distorted Segregation Ratio of Mating Types Among Basidiospores in Lentinula edodes

This study prepared 17 strains of Lentinula edodes , including wild and cultivated strains as materials, and statistically analyzed the ratios of spores from different aspects via mating types' analysis and the OWE-SOJ technique. The results from this study first systematically identified skewed expected distribution of mating-type factors segregation in Lentinula edodes spores has commonly statistical meanings in wild and cultivated strains. Genetic analysis of positive and negative parental-recombined fruiting showed that the nuclear type of F 1 progeny spores among those strains segregated through theoretical distribution mainly depended on the combined state of parental dikaryons, and the predominant spores were those with the mating type identical to the dikaryotic parent, indicating that the genetic basis of segregation distortion of spores is different from that of protoplast monokaryons in which the B factor takes predominant responsibility for that phenomenon, and it cooperates A factor with B factor to influence the ratio of spores.

Segregation distortion of wild-type alleles at the Machado-Joseph disease locus: a study in normal families from the Azores islands (Portugal)

Machado-Joseph disease (MJD) is caused by an expansion of a triplet repeat with a CAG motif at the ATXN3 gene. The putative segregation ratio distortion (SRD) of alleles can play an important role in the non-Mendelian behaviour of triplet repeat loci. To study the stability and infer the segregation patterns of wild-type MJD alleles, the size of the (CAG)(n) tract was analysed in 102 normal sibships, representing 428 meioses. No mutational events were detected during the transmission of alleles. Segregation analysis showed that the smaller alleles were preferentially transmitted (56.9%). Considering maternal meioses alone, such preference was still detected (55.7%) but without statistical significance. A positive correlation was observed for the difference in length between the two alleles constituting the transmitters' genotype (D) and the frequency of transmission of the smaller alleles. The results suggest that small D values are not enough to modify the probability of allele transmission. When transmissions involving genotypes with D <or= 2 were excluded, SRD in favour of the smaller allele became significant for both maternal and paternal transmissions. Therefore, the genotypic composition of the transmitters in a sample to be analysed should influence the ability to detect SRD, acting as a confounding factor.

An EM algorithm for mapping segregation distortion loci

BackgroundChromosomal region that causes distorted segregation ratios is referred to as segregation distortion locus (SDL). The distortion is caused either by differential representation of SDL genotypes in gametes before fertilization or by viability differences of SDL genotypes after fertilization but before genotype scoring. In both cases, observable phenotypes are distorted for marker loci in the chromosomal region close to the SDL. Under the quantitative genetics model for viability selection by proposing a continuous liability controlling the viability of individual, a simplex algorithm has been used to search for the solution in SDL mapping. However, they did not consider the effects of SDL on the construction of linkage maps.ResultsWe proposed a multipoint maximum-likelihood method to estimate the position and the effects of SDL under the liability model together with both selection coefficients of marker genotypes and recombination fractions. The method was implemented via an expectation and maximization (EM) algorithm. The superiority of the method proposed under the liability model over the previous methods was verified by a series of Monte Carlo simulation experiments, together with a working example derived from the MAPMAKER/QTL software.ConclusionOur results suggested that the new method can serve as a powerful alternative to existing methods for SDL mapping. Under the liability model, the new method can simultaneously estimate the position and the effects of SDL as well as the recombinant fractions between adjacent markers, and also be used to probe into the genetic mechanism for the bias of uncorrected map distance and to elucidate the relationship between the viability selection and genetic linkage.

Evidence of a segregation ratio distortion of SMN1 alleles in spinal muscular atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterised by degeneration and loss of the motor neurons of the anterior horn of the spinal cord. The absence of SMN1 is determinant to have SMA and parents of SMA patients are regarded as carriers of the disease. We compared the segregation ratio of the mutated allele and the wild-type allele of all the confirmed carrier parents assuming Mendelian proportions. Results of transmissions in 235 prenatal tests and in 128 unaffected siblings showed a statistically significant deviation in favour of the wild-type SMN1 allele. The number of affected foetuses and carriers were lower than that expected. No significant differences in the sex ratio or in the progenitor origin of the transmitted allele to the carriers were found. One hypothesis that has been advanced to account for the distortion observed in affected foetuses is the negative postzygote selection due to early miscarriage. However, given that the number of carriers in our series was lower than expected, prezygote events such as meiotic drive, survival of gametes or preferential fertilisation should also be considered.