Variation in the expressivity of the ocular retardation gene in mice

Variation in the expressivity was studied of the gene for ocular retardation (or) in mice. It is shown that the gene or suppresses with a high expressivity the growth of the optic vesicle in homozygotes, this resulting in anophthalmia and microphthalmia with aphakia. In cases of low expressivity, the gene or inhibits the growth of retina anlage, this leading to microphthalmia with a cataract of the lens. Variation in the expressivity of the gene or is due to an influence of modifier genes.     

Somatic mosaicism and variable expressivity

For more than 50 years geneticists have assumed that variations in phenotypic expression are caused by alterations in genotype. Recent evidence shows that 'simple' mendelian disorders or monogenic traits are often far from simple, exhibiting phenotypic variation (variable expressivity) that cannot be explained entirely by a gene or allelic alteration. In certain cases of androgen insensitivity syndrome caused by identical mutations in the androgen receptor gene, phenotypic variability is caused by somatic mosaicism, that is, somatic mutations that occur only in certain androgen-sensitive cells. Recently, more than 30 other genetic conditions that exhibit variable expressivity have been linked to somatic mosaicism. Somatic mutations have also been identified in diseases such as prostate and colorectal cancer. Therefore, the concept of somatic mutations and mosaicism is likely to have far reaching consequences for genetics, in particular in areas such as genetic counseling.     

Penetrance and expressivity of the gene for double podding in chickpea

The double-pod per peduncle trait is known to contribute to increased seed yield in chickpea (Cicer arietinum L.). A cross was made between the single-podded variety ICCV 2 and the double-podded variety JG 62 in 1993. Penetrance and expressivity of the gene for double podding was studied in an F2 population and F10 recombinant inbred lines (RILs) of this cross. Homozygous recessive allele of this gene (ss) governs the production of double flowers and pods per peduncle. Results indicated that the s allele has unstable penetrance and variable expressivity. The penetrance of this allele was 53% for the F2 and 84.5% for the RILs. The ranges for the expression of this trait among the penetrant F2 individuals and the penetrant RILs were 1.1-14.8% and 0.1-33.0%. These were 8.3-30.8% for early sown and 17.1-68.7% for the late sown double-podded parent JG 62. Thus it appears that the allele shows greater penetrance and enhanced expressivity under soil moisture stress. In the F2 the seed yield advantage of the double-podded over the single-podded plants was 18%, whereas among the RILs it was 7%. The increased number of pods and seeds contributed to the higher yield. However, there was a slight decrease in seed size of the double-podded genotypes. An increase in the size of seed may have a role in the decreased penetrance and expressivity of this allele among the double-podded segregants of the ICCV 2 x JG 62 chickpea cross.     

Emotional expressivity as a signal of cooperation

Previous research has suggested that the spontaneous display of positive emotion may be a reliable signal of cooperative tendency in humans. Consistent with this proposition, several studies have found that self-reported cooperators indeed display higher levels of positive emotions than non-cooperators. In this study, we defined cooperators and non-cooperators in terms of their behavior as the proposer in an ultimatum game, and video-taped their facial expressions as they faced unfair offers as a responder. A detailed analysis of the facial expressions displayed by participants revealed that cooperators displayed greater amounts of emotional expressions, not limited to positive emotional expression, when responding to unfair offers in the ultimatum game. These results suggest that cooperators may be more emotionally expressive than non-cooperators. We speculate that emotional expressivity can be a more reliable signal of cooperativeness than the display of positive emotion alone.     

Bartsocas-Papas syndrome with variable expressivity in an Egyptian family

Bartsocas-Papas syndrome (BPS) is an autosomal recessively inherited sublethal popliteal pterygium condition characterized by intrauterine or neonatal death, severe popliteal webbing, oligosyndactyly, ankyloblepharon, orofacial clefts, intraoral filiform bands and genital anomalies. Internal organ involvement has seldom been identified. We report on a 3 years old female patient of healthy first cousin parents with BPS. She presented with orofacial clefting, severe popliteal webs, club feet, oligosyndactyly of the toes, hypogenitalism and normal hands and internal organs. Ankyloblepharon and filiform bands between the alveolar ridges were evident at birth. Pedigree analysis revealed a more severely affected female sib, who died a few minutes after birth with additional manifestations including near complete lip fusion without oral cleft, complete syndactyly in both hands and an omphalocele. Linkage was excluded to the IRF6 gene; a candidate gene implicated in the Van der Woude and popliteal pterygium syndromes, with overlapping features with BPS. To our knowledge, this is the 5th surviving patient with this syndrome in the literature. In this report, we also discuss the proposed pathogenetic mechanisms for BPS and compare our patients with similarly described cases as well as overlapping spectrum of other popliteal pterygium syndromes. Our findings provide further evidence of intrafamilial clinical heterogeneity in families with BPS.     

Codon usage in bacteria: correlation with gene expressivity

The nucleic acid sequence bank now contains over 600 protein coding genes of which 107 are from prokaryotic organisms. Codon frequencies in each new prokaryotic gene are given. Analysis of genetic code usage in the 83 sequenced genes of the Escherichia coli genome (chromosome, transposons and plasmids) is presented, taking into account new data on gene expressivity and regulation as well as iso-tRNA specificity and cellular concentration. The codon composition of each gene is summarized using two indexes: one is based on the differential usage of iso-tRNA species during gene translation, the other on choice between Cytosine and Uracil for third base. A strong relationship between codon composition and mRNA expressivity is confirmed, even for genes transcribed in the same operon. The influence of codon use of peptide elongation rate and protein yield is discussed. Finally, the evolutionary aspect of codon selection in mRNA sequences is studied.     

Variable expressivity of the tumour suppressor protein TRP53 in cryopreserved human blastocysts

In a mouse model, in vitro fertilization or extended embryo culture leads to the increased expression of TRP53 in susceptible embryos. Ablation of the TRP53 gene improved embryo viability indicating that increased expression of TRP53 is a cause of the reduction of embryo viability resulting from in vitro fertilization or embryo culture. This study investigates the status of TRP53 expression in human embryos produced by intracytoplasmic sperm injection. Following fertilization, embryos were cultured for 96 h and then cryopreserved. Immediately upon thawing they were fixed in formaldehyde and subjected to immunostaining for TRP53. Staining was visualized by confocal microscopy. Negative controls were incubated with isotype control immunoglobulin and showed negligible staining. All embryos showed TRP53 staining above negative controls. TRP53 staining was heterogenous within and between embryos. An embryo that showed retarded development showed high levels of TRP53 expression. A blastocyst that had a collapsed blastocoel also showed high levels of TRP53 compared to morphologically normal blastocysts. Most TRP53 staining was in the region of the nucleus. Morphologically normal blastocysts tended to show little nuclear accumulation of stain. However, some cells within these embryos had high levels of nuclear TRP53 expression. The results show that embryos have varying sensitivity to the stresses of production and culture in vitro, and this resulted in variable expressivity of TRP53.     

The joint distribution of patterns in random sequences with application to the RC-measure for expressivity

A method previously developed for computation of pattern probabilitiesin random sequences under Markov chain models. We extend thismethod to the calculation of the joint distribution for twopatterns. An application yields the distribution of the rightchoice measure for expressivity and how significance boundsdepend on sequence length. These bounds are used to show thatthe choice of pyrimidine in codon position 3 of Escherichiacoli genes deviates considerably from a general Markov processmodel for coding regions. We also derive some statistical evidencethat this significant deviation is limited to codon position3.     

Hereditary retinoblastoma: Penetrance,expressivity and age of onset

Summary Analyses of family data published in Japan concerning 29 kindreds with 2 or more cases of retinoblastoma revealed that, in the children who received the gene from a carrier parent, both penetrance and expressivity increase with increasing degree of expressivity in the parent. The estimate for the average degree of penetrance varies from 0.7 to 0.9, depending upon the method employed. The value will be increased with increasing number of survivors of hereditary retinoblastoma. Data were presented to indicate that the hereditary form of retinoblastoma onset tends to be later in unilateral than in bilateral affection, though in the non-hereditary form onset will be further delayed. No effect of birth order was detected. It was suggested that suppressor genes at other loci play a significant role in manifestation of the major dominant gene for retinoblastoma. Implications of these findings were discussed.This work, contribution number 1093 from the National Institute of Genetics, was supported by grants-in-aid from the Ministry of Education and the Ministry of Health and Welfare.     

Genetic basis of a spontaneous mutation’s expressivity

Genetic background often influences the phenotypic consequences of mutations, resulting in variable expressivity. How standing genetic variants collectively cause this phenomenon is not fully understood. Here, we comprehensively identify loci in a budding yeast cross that impact the growth of individuals carrying a spontaneous missense mutation in the nuclear-encoded mitochondrial ribosomal gene MRP20. Initial results suggested that a single large effect locus influences the mutation’s expressivity, with 1 allele causing inviability in mutants. However, further experiments revealed this simplicity was an illusion. In fact, many additional loci shape the mutation’s expressivity, collectively leading to a wide spectrum of mutational responses. These results exemplify how complex combinations of alleles can produce a diversity of qualitative and quantitative responses to the same mutation.     

Gene expressivity is the main factor in dictating the codon usage variation among the genes in Pseudomonas aeruginosa

Codon usage biases of all DNA sequences (length greater than or equal to 300 bp) from the complete genome of Pseudomonas aeruginosa have been analyzed. As P. aeruginosa is a GC-rich organism, G and/or C are expected to predominate in their codons. Overall codon usage data analysis indicates that indeed codons ending in G and/or C are predominant in this organism. But multivariate statistical analysis indicates that there is a single major trend in the codon usage variation among the genes in this organism, which has a strong negative correlation with the expressivities of the genes. The majority of the lowly expressed genes are scattered towards the positive end of the major axis whereas the highly expressed genes are clustered towards the negative end. This is the first report where the prokaryotic organism having highly skewed base composition is dictated mainly by translational selection, though some other factors such as the lengths of the genes as well as the hydrophobicity of genes also influence the codon usage variation among the genes in this organism in a minor way.     

Bioinformatic analysis of the link between gene composition and expressivity in Saccharomyces cerevisiae and Schizosaccharomyces pombe

The compositional non-randomness was studied in genes of Saccharomyces cerevisiae and Schizosaccharomyces pombe. In both species, codon usage is well correlated with expressivity (measured as the codon adaptation index). Both species generally display higher nucleotide non-randomness in the group of highly expressed genes than in the lowly expressed genes. The highly expressed genes in both species are furthermore characterized by marked peaks in non-randomness at N=3 upstream of start codons, N=2 downstream of start codons and at N=1 and N=7 downstream of stop codons, indicating that these nucleotides may be key elements in translational regulation. Intragenic variation in codon usage was also observed to be linked to expressivity. It is suggested that the firm link between expressivity and codon usage calls for codon optimization. Based on bioinformatic calculations, examples of proteins are given for which codon optimizations might be relevant.     

The cis-trans effects of crossing-over on the penetrance and expressivity of dominantly inherited disorders

A surprisingly simple model based on the cis-trans effects of meiotic and mitotic crossing-over is proposed to explain apparent non-penetrance and reduced expressivity in dominantly inherited disorders. Sex differences, discordant monozygotic twins, multifactorial inheritance and allelism are also discussed.