Segregation Frequency Research Articles

Concordance and recessive inheritance of Leber congenital amaurosis.

Pedigrees were obtained on 43 patients with confirmed Leber congenital amaurosis, a rare form of blindness caused by congenital dysfunction of the retina. All of the pedigrees were consistent with autosomal recessive inheritance and the segregation frequency using classical segregation analysis was 0.24 +/- 0.07. Six of the 7 affected sib pairs were concordant in regards to systemic abnormalities. Despite previous reports that Leber congenital amaurosis can be inherited either as an autosomal dominant or recessive condition, our findings support only an autosomal recessive inheritance of this disorder.

Formation of multiple embryo-like structures from single microspores during maize anther culture

In a previous study on the RFLP analysis of the maize anther culture response (Wan et al. 1992), some of the anther-derived callus Unes from hybrids H99 x Pa91 (HP) and H99 x FR16 (HF) showed the same RFLP patterns with 58 (for HP Unes) or 35 (for HF lines) RFLP markers used. Since the callus Unes with the identical RFLP pattern were initiated from individual embryo-like structures (ELSs) from the same anther culture plate, these must have originated from the same microspore. Twin embryos which apparently had originated from the same microspore were also observed. Thus in certain cases one microspore must be capable of forming more than one ELS. However, in the case of the callus Unes from a different F1 hybrid (Pa91 x FR16), no identical RFLP patterns were observed. Thus multiple ELS formation from a single microspore may be genetically controlled. Since in some cases the proportion of callus lines resulting from multiple ELS formation can be quite high (about 50% for the HP lines), estimates of gene segregation and anther culture response frequencies can be affected greatly.

Genetic transmission of colorectal cancer: exploratory data analysis from a population based registry.

Classical segregation analysis was conducted on 605 families of probands with colorectal carcinoma ascertained through the Cancer Registry of the Province of Modena in Italy. The families were classified as 28 suspected hereditary non-polyposis colorectal cancer (HNPCC) syndromes and 577 presumed non-HNPCC. In 11 of these, both parents had colorectal carcinoma, in 130 one parent was affected, and in 436 both parents were normal. In the suspected HNPCC families, segregation was compatible with dominant transmission of susceptibility to carcinoma. In families with one parent affected, the segregation frequency was almost exactly equal to the frequency of segregation in families where both parents were normal. The model of dominant transmission of susceptibility through a major gene with greatly reduced penetrance in heterozygotes fitted the data acceptably.

Formation of first division restitution (FDR) 2n-megaspores through pseudohomotypic division in ds-1 (desynapsis) mutants of diploid potato: routine production of tetraploid progeny from 2xFDR × 2xFDR crosses

The level and mode of 2n megaspore formation was studied in full-sib diploid potato clones with either normal or desynaptic (ds-1ds-1) meiosis. Cytological analysis revealed that functional 2n megaspores produced by normal and desynaptic clones originate exclusively from 'second division restitution (SDR)' and 'first division restitution (FDR)', respectively. SDR 2n megaspores resulted from the omission of the second meiotic division following chromosome doubling after anaphase I, whereas FDR 2n megaspores resulted from a direct equational division of univalent chromosomes at anaphase I (pseudohomotypic division). Comparative data strongly indicated that the observed mechanisms of SDR and FDR 2n megaspore formation are extremes of a continuum that is being brought about by common genes for precocious chromosome division. Depending on the relative timing of cell cycle and chromosome division, this precocious chromosome division may impose postreductional (SDR) or prereductional (FDR) 'restitution' of the sporophytic chromosome number under normal synaptic and desynaptic conditions, respectively. The observed frequencies of 2n megaspores closely correlated with seed set, following pollination by tetraploid varieties and by desynaptic diploid clones with exclusive FDR 2n pollen formation. Up to 54.0 and 21.5 seeds/ fruit were obtained from normal synaptic (SDR) and desynaptic (FDR) progeny, respectively. The high frequency of segregants with either SDR or FDR 2n megaspore formation (78.0 and 45.2%, respectively) supports the hypothesis that sexual polyploidization is the driving force behind the origin and evolution of polyploid Solanum species. The present identification of diploid potato clones with consistent FDR 2n megaspore formation extends the opportunities for direct transfer of enhanced diploid germ plasm to tetraploids, and particularly advocates the feasibility of 2x(ds-1; FDR)×2x(ds-1; FDR) breeding schemes in cultivar development and the production of relatively vigorous and uniform true potato seed (TPS) varieties. Its potential value and limitations for breeding and the experimental induction of diplosporic apomixis are discussed.

The chromosomal constitution of wine strains of Saccharomyces cerevisiae

A general procedure is described for determining the chromosomal constitution of industrial strains of Saccharomyces cerevisiae based on analysis of segregation frequencies for input markers among random spore progeny of industrial-laboratory strain hybrids. The multiply auxotrophic haploid testers used carried a dominant erythromycin-resistance marker, allowing hybrids to be selected in mass matings with spores produced by the wild-type industrial strains. Analysis of a number of independent crosses between the haploid testers and an unselected population of spores of each wine strain distinguished between disomic, trisomic and tetrasomic chromosomal complements in the parents. Possible explanations for a significant class of aberrant segregation frequencies are discussed. Results of the analysis indicate that UCD Enology 522 (Montrachet) is diploid and possibly trisomic for chromosome VII; 522X is diploid; UCD Enology 505 (California Champagne) is disomic for chromosome XVI, trisomic for chromosomes I, II, III, VI, VIII, IX, X, XII, XV, tetrasomic for chromosomes IV, XI, XIII, XIV and either trisomic or tetrasomic for chromosomes V and VII; and that UCD Enology 595 (Pasteur Champagne) is disomic for chromosomes I, II, III, IX, XVI, trisomic for chromosomes IV, VI, X, XII, XIV, XV, tetrasomic for chromosomes V, VIII, XI, XIII and either disomic or tetrasomic for chromosome VII.

Segregation analysis of 1885 DMD families: significant departure from the expected proportion of sporadic cases

The proportion of sporadic cases of Duchenne muscular dystrophy has been estimated by classical segregation analysis in a pooled sample of 1885 sibships from 7 different countries. A significant departure from the theoretical expectations based on mutation-selection equilibrium is observed (segregation frequency = 0.439 +/- 0.017; frequency of sporadic cases = 0.229 +/- 0.026, at the maximum likelihood). The occurrence of germinal mosaicism in some of the mothers of Duchenne cases may account for this peculiar finding, although a possible role of inequality of mutation rates in the two sexes cannot be ruled out.

Genetic analysis of Aspergillus niger: Isolation of chlorate resistance mutants, their use in mitotic mapping and evidence for an eighth linkage group

This paper describes the use of chlorate resistant mutants in genetic analysis of Aspergillus niger. The isolated mutants could be divided into three phenotypic classes on the basis of nitrogen utilization. These were designated nia, nir and cnx as for Aspergillus nidulans. All mutations were recessive to their wild-type allele in heterokaryons as well as in heterozygous diploids. The mutations belong to nine different complementation groups. In addition a complex overlapping complementation group was found. Evidence for the existence of eight linkage groups was obtained. Two linked chlorate resistance mutations and two tryptophan auxotrophic markers, which were unlinked to any of the known markers, form linkage group VIII. We used the chlorate resistance mutations as genetic markers for the improvement of the mitotic linkage map of A. niger. We determined the linear order of three markers in linkage group VI as well as the position of the centromere by means of direct selection of homozygous cnxA1 recombinants. In heterozygous diploid cultures diploid chlorate resistant segregants appeared among conidiospores with a frequency of 3.9 x 10(-5) (cnxG13 in linkage group I) to 2.1 x 10(-2) (cnxD6 in linkage group III). The mean frequency of haploid chlorate resistant segregants was 1.3 x 10(-3). The niaD1 and niaD2 mutations were also complemented by transformation with the A. niger niaD+ gene cloned by Unkles et al. (1989). Mitotic stability of ten Nia+ transformants was determined. Two distinct stability classes were found, showing revertant frequencies of 5.0 x 10(-3) and 2.0 x 10(-5) respectively.

Selection at the ABO locus in the Japanese population.

Hiraizumi et al. (1973b) concluded that maternal-fetal ABO incompatibility effect upon the frequency of prenatal deaths was totally absent in two modern Japanese cities, Ohdate and Akita. However, they found a significant heterogeneity in the frequency of prenatal deaths among 16 mating types and suggested that the viability of A-bearing fetuses was higher than that of others, hence the frequency of prenatal deaths decreased with the increasing probability of producing A-bearing fetuses. Further analyses were performed in the present study and the above suggestion was confirmed. Then, the average numbers of prenatal deaths and pregnancies per couple were analyzed separately for their relationships with the probability of producing an A-bearing fetus. The results were found to be consistent with the model that the average numbers of prenatal losses per couple are approximately the same between two groups of matings, one producing and the other not producing A-bearing fetuses, but such losses occur more frequently for the A-bearing fetuses than others at the very early stage of pregnancy such that wives may not recognize such losses. Although the stages of losses are different between A-bearing and other fetuses, the net losses are nearly the same between them, so that such losses will not be reflected in the segregation frequencies among children, as shown by Hiraizumi et al. (1973a).

The predictive value of quantitative genetic parameters in autogamous crops: Bias caused by intergenotypic competition. 1. F∞-mean

Quantitative genetic theory for autogamous crops enables the estimation of the parameters m (F∞-mean) and D (F∞-variance) in the F3-generation. With these estimated m and D a prediction can be made of the probability of finding superior inbred lines in the F∞-offspring of the cross. The accuracy of this procedure is influenced by the correctness of the genetic model, by the magnitude of the error variance, and by the bias caused by intergenotypic competition, which is present in the environment in which the F3 is grown and absent in the monoculture environment at which the selection is aimed, especially in a cereal crop like wheat. The influence of the intergenotypic competition was investigated by a special method of simulating segregating populations. In this method genotypes in the offspring of a cross are represented by varieties and segregating populations are composed by mixing the appropriate varieties according to the proper segregation frequencies. Growing the simulated population enables the estimation of m and D in the normal selection environment, while simultaneously growing the varieties in a large monoculture trial enables the calculation of ‘true’ values of m and D in the monoculture environment. Hence, a comparison is possible.

Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.

In vitro-constructed heteroduplex DNAs with defined mismatches were corrected in Saccharomyces cerevisiae cells with efficiencies that were dependent on the mismatch. Single-nucleotide loops were repaired very efficiently; the base/base mismatches G/T, A/C, G/G, A/G, G/A, A/A, T/T, T/C, and C/T were repaired with a high to intermediate efficiency. The mismatch C/C and a 38-nucleotide loop were corrected with low efficiency. This substrate specificity pattern resembles that found in Escherichia coli and Streptococcus pneumoniae, suggesting an evolutionary relationship of DNA mismatch repair in pro- and eucaryotes. Repair of the listed mismatches was severely impaired in the putative S. cerevisiae DNA mismatch repair mutants pms1 and pms2. Low-efficiency repair also characterized pms3 strains, except that correction of single-nucleotide loops occurred with an efficiency close to that of PMS wild-type strains. A close correlation was found between the repair efficiencies determined in this study and the observed postmeiotic segregation frequencies of alleles with known DNA sequence. This suggests an involvement of DNA mismatch repair in recombination and gene conversion in S. cerevisiae.

Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.

In vitro-constructed heteroduplex DNAs with defined mismatches were corrected in Saccharomyces cerevisiae cells with efficiencies that were dependent on the mismatch. Single-nucleotide loops were repaired very efficiently; the base/base mismatches G/T, A/C, G/G, A/G, G/A, A/A, T/T, T/C, and C/T were repaired with a high to intermediate efficiency. The mismatch C/C and a 38-nucleotide loop were corrected with low efficiency. This substrate specificity pattern resembles that found in Escherichia coli and Streptococcus pneumoniae, suggesting an evolutionary relationship of DNA mismatch repair in pro- and eucaryotes. Repair of the listed mismatches was severely impaired in the putative S. cerevisiae DNA mismatch repair mutants pms1 and pms2. Low-efficiency repair also characterized pms3 strains, except that correction of single-nucleotide loops occurred with an efficiency close to that of PMS wild-type strains. A close correlation was found between the repair efficiencies determined in this study and the observed postmeiotic segregation frequencies of alleles with known DNA sequence. This suggests an involvement of DNA mismatch repair in recombination and gene conversion in S. cerevisiae.

Segregation frequency in microcephaly

A total of 118 cases of microcephaly were clinically evaluated under two main groups: primary microcephaly (61 cases) and secondary microcephaly (57 cases). Secondary cases were generally characterized by convulsions, spasticity, and other congenital anomalies. Estimates of segregation frequency obtained separately in primary and secondary cases indicated that the primary consanguineous cases were most probably due to a single recessive gene. The segregation frequency was substantially less in other types, indicating much lower genetic risks in these cases.

Mutations in CEN3 cause aberrant chromosome segregation during meiosis in Saccharomyces cerevisiae.

We investigated the structural requirements of the centromere from chromosome III (CEN3) of Saccharomyces cerevisiae by analyzing the ability of chromosomes with CEN3 mutations to segregate properly during meiosis. We analyzed diploid cells in which one or both copies of chromosome III carry a mutant centromere in place of the wild-type centromere and found that some alterations in the length, base composition and primary sequence characteristics of the central A+T-rich region (CDE II) of the centromere had a significant effect on the ability of the chromosome to segregate properly through meiosis. Chromosomes containing mutations which delete a portion of CDE II showed a high rate of premature disjunction at meiosis I. Chromosomes containing point mutations in CDE I or lacking CDE I appeared to segregate properly through meiosis; however, plasmids carrying centromeres with CDE I completely deleted showed an increased frequency of segregation to nonsister spores.

TRANSMISSION GENETICS OF ISOZYME LOCI IN RAPHANUS SATIVUS (BRASSICACEAE): STRESS‐DEPENDENT NON‐MENDELIAN SEGREGATION

Deviations from Mendelian ratios are frequently treated as an intrinsic property of individuals, independent of the environment. We tested whether the environment of the parents could alter patterns of inheritance in the wild radish, Raphanus sativus. We demonstrated the genetic basis of 12 isozyme loci by controlled pollinations of unstressed plants. The frequency of deviant segregation detected was not different than that expected by chance. Controlled pollinations among stressed plants showed over 3 times as much deviant segregation as the unstressed controls. No genetic correlates of segregation bias were detected. Linkage was assessed for 64 of the 66 pairs of loci. Two linkage groups were detected, one involving four loci (PGM2–ACO–ACP–LAP), the other involving a single pair (EST‐PRX). The second linkage group is apparently associated with a locus or tightly linked loci which may segregate for “balanced” lethals on the same chromosome. Deviant segregation did not appear to act primarily by selection on a particular gamete. Postzygotic selection was the probable source of at least some of the aberrant segregation. Because no particular allele was favored in such situations, selection is apparently operating on alleles at linked loci rather than on the allozyme loci per se. Data from other studies on wild radish support the suggestion that postzygotic selection might be an important influence on progeny segregation ratios. Because wild radishes often encounter a variety of stresses in the field, in this species, aberrant segregation may be common under natural conditions.

Transmission Genetics of Isozyme Loci in Raphanus sativus (Brassicaceae): Stress-Dependent Non-Mendelian Segregation

Deviations from Mendelian ratios are frequently treated as an intrinsic property of individuals, independent of the environment. We tested whether the environment of the parents could alter patterns of inheritance in the wild radish, Raphanus sativus. We demonstrated the genetic basis of 12 isozyme loci by controlled pollinations of unstressed plants. The frequency of deviant segregation detected was not different than that expected by chance. Controlled pollinations among stressed plants showed over 3 times as much deviant segregation as the unstressed controls. No genetic correlates of segregation bias were detected. Linkage was assessed for 64 of the 66 pairs of loci. Two linkage groups were detected, one involving four loci (PGM2–ACO–ACP–LAP), the other involving a single pair (EST-PRX). The second linkage group is apparently associated with a locus or tightly linked loci which may segregate for “balanced” lethals on the same chromosome. Deviant segregation did not appear to act primarily by selection on a particular gamete. Postzygotic selection was the probable source of at least some of the aberrant segregation. Because no particular allele was favored in such situations, selection is apparently operating on alleles at linked loci rather than on the allozyme loci per se. Data from other studies on wild radish support the suggestion that postzygotic selection might be an important influence on progeny segregation ratios. Because wild radishes often encounter a variety of stresses in the field, in this species, aberrant segregation may be common under natural conditions.

Orientation and segregation of Robertsonian trivalents in Dichroplus pratensis (Acrididae).

Pairing behavior, metaphase I orientation, and anaphase I segregation of centric fusion trivalents were studied in 26 single, 15 double, and 2 triple male fusion heterozygotes of the polymorphic South American melanopline grasshopper Dichroplus pratensis. They represent the seven different fusions and their combinations already described in different populations of the species. Our analysis showed the following: (1) pairing behavior is very regular in all trivalents; (2) frequencies of linear orientation was very low irrespective of the trivalent involved; (3) reorientation seems to occur frequently since frequencies of abnormal segregation and aneuploid second division cells were invariably lower than those of nonconvergent orientation; (4) aneuploidy and abnormal sperm production increases with increasing number of fusions; (5) chiasma frequency and localisation is relevant to trivalent orientation since trivalents with nonconvergent orientations showed proximal and interstitial chiasmata more frequently than convergently oriented ones. The results are in agreement with the hypothesis that these polymorphisms are old and stable, and confirm that for the maintenance of a balanced polymorphism, if this polymorphism is adaptive because of its consequences on recombination, position effects, etc., changes tending to stabilise trivalent orientation and segregation are central.

Homozygous and heterozygous homologous chromosomes: effects on preferential pairing and recombination frequency in wheat

Trisomics for chromosomes 1A and 6B of wheat backcrossed to euploids showed progeny with unexpected segregation frequencies (cytological and genetical) that can be attributed to preferential pairing between homologues. Recombination frequency between the centromere and a gene for mildew reaction of chromosome 1A showed an increase from the first to the second backcross that could be attributed to a positive correlation between homozygosity and the degree of pairing between homologous chromosomes. The use of wheat trisomics for genetic analysis is also discussed.Key words: preferential pairing, trisomic segregation, wheat cytogenetics, recombination frequency, pathogen reaction.

Investigation of the segregation of the fragile X mutation in daughters of obligate carrier women.

Two reports have suggested that over 50% of the offspring of obligate carrier women receive the mutation for the fra(X) or the Martin-Bell syndrome [Webb et al, 1986; Fryns, 1984]. Such a segregation distortion is difficult to assess for the fra(X) syndrome because of incomplete penetrance, variable expression and probable ascertainment biases. We have attempted to evaluate this possible segregation distortion in daughters of obligate carriers in a large sample of sibships ascertained in a survey of New South Wales, Australia. We used two definitions of expression: 1) presence of fra(X) positive cells if daughters were tested cytogenetically, and 2) mental impairment if daughters were not tested cytogenetically. The segregation frequency was estimated in different types of sibships of obligate carriers based on the way they were ascertained. This was done in order to have an internal check on possible ascertainment biases. Among the 189 cytogenetically tested daughters, 81 were fra(X) positive. Among the 97 untested daughters, 24 were mentally impaired in some way. Therefore, the segregation frequency as defined by fra(X) expression and/or mental impairment was 37%. Thus, no evidence was detected for segregation distortion. These data were significantly different than those collected by Webb et al [1986] and scored by the same method as the present data set.

A DNA Sequence Conferring High Postmeiotic Segregation Frequency to Heterozygous Deletions in Saccharomyces cerevisiae is Related to Sequences Associated with Eucaryotic Recombination Hotspots

The meiotic behavior of two graded series of deletion mutations in the ADE8 gene in Saccharomyces cerevisiae was analyzed to investigate the molecular basis of meiotic recombination. Postmeiotic segregation (PMS) was observed for a subset of the deletion heterozygosities, including deletions of 38 to 93 base pairs. There was no clear relationship between deletion length and PMS frequency. A common sequence characterized the novel joint region in the alleles which displayed PMS. This sequence is related to repeated sequences recently identified in association with recombination hotspots in the human and mouse genomes. We propose that these particular deletion heterozygosities escape heteroduplex DNA repair because of fortuitous homology to a binding site for a protein.

A DNA sequence conferring high postmeiotic segregation frequency to heterozygous deletions in Saccharomyces cerevisiae is related to sequences associated with eucaryotic recombination hotspots.

The meiotic behavior of two graded series of deletion mutations in the ADE8 gene in Saccharomyces cerevisiae was analyzed to investigate the molecular basis of meiotic recombination. Postmeiotic segregation (PMS) was observed for a subset of the deletion heterozygosities, including deletions of 38 to 93 base pairs. There was no clear relationship between deletion length and PMS frequency. A common sequence characterized the novel joint region in the alleles which displayed PMS. This sequence is related to repeated sequences recently identified in association with recombination hotspots in the human and mouse genomes. We propose that these particular deletion heterozygosities escape heteroduplex DNA repair because of fortuitous homology to a binding site for a protein.