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BRCA1 mutations have been identified in breast and ovarian cancer families from diverse ethnic backgrounds. We studied 17 different families with the BRCA1 2800delAA mutation; seven were ascertained in Scotland (Dundee, Edinburgh, Glasgow, St Andrews), five in Canada (Toronto, Victoria) and five in the United States (Chicago, Philadelphia, Seattle). Overall there was a clear preponderance of Scottish ancestry. Genotype analysis performed on key members from 17 families was consistent with a common haplotype, strongly suggesting a single ancestral origin. A possible link was established between two families by tracing their genealogies through the records of the Registrar General for Scotland. This is the first example of a BRCA1 mutation likely to be derived from a common founder in Scotland. Further studies will be necessary to estimate more accurately the population frequency of the BRCA1 2800delAA mutation among unselected cases of breast and ovarian cancer in Scotland and the UK. [ABSTRACT FROM AUTHOR]

In a prospective study of 466 X chromatin positive males an increase in mortality of about 50% has been observed. The increase is associated with a loss of about five years in life span. There is no convincing evidence that the increase is concentrated at any particular age group but this possibility could not be excluded. No effect of mode of ascertainment could be demonstrated. From this study we conclude that it is likely that the mortality experienced by chromatin positive males in general is at least 115% of that experienced by normal men and could be more than 200%. [ABSTRACT FROM AUTHOR]

Data on the families of 74 probands with autopsy-proven Alzheimer's disease did not support the hypothesis, advanced by Heston and co-workers, of a familial association between Alzheimer's disease, Down's syndrome and immunoproliferative disorders. However, there are difficulties of interpreting negative conclusions in this type of study, particularly those resulting from small sample size and the impossibility of tracing all relatives; only the data for immunoproliferative disorders are incompatible with the hypothesis, those for Down's syndrome being too few to be informative. The incidence of presenile dementia among the first-degree relatives of probands was raised, as in many previous studies, and was consistent with a simple polygenic model. The mean parental age at birth of the probands was significantly raised by about 2 years (P divided by 0.01), but so also was that of their unaffected sibs, suggesting that the mechanism differs from that occurring in trisomy 21 and certain other aneuploidies. [ABSTRACT FROM AUTHOR]

Time-delayed optical feedback is known to trigger a wide variety of complex dynamical behavior in semiconductor lasers. Adding a second optical feedback loop is naturally expected to further increase the complexity of the system and its dynamics, but due to interference between the two feedback arms, it was also quickly identified as a way to improve the laser stability. While these two aspects have already been investigated, the influence of the feedback phases, i.e., sub-wavelength changes in the mirror positions, on the laser behavior still remains to be thoroughly studied, despite indications that this parameter could have a significant impact. Here, we analyze the effect of the feedback phase on the laser stability in a dual-feedback configuration. We show an increased sensitivity of the laser system to feedback phase changes when two-feedback loops are present and clarify the interplay between the frequency shift induced by the feedback and the interferometric effect between the two feedback arms., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

There are many reports of familial aggregation in stroke. However, whether familial aggregation is largely due to genetic or environmental factors is not established. Consecutive subjects with stroke were matched with 2 controls per case of the same sex, born in the same year, district, and whose fathers had the same occupation. Presence on parental death certificates of cerebrovascular disease, other vascular disease, bronchial carcinoma, hypertension, diabetes mellitus and other causes of death was recorded. No significant difference in risk was found for cases having mother (odds ratio, OR 1.08, 95% confidence interval, CI, 0.74-1.57), father (OR 0.91, 95% CI 0.58-1.45) or either parent (OR 1.04, 95% CI 0.74-1.46) with cerebrovascular disease. Familial aggregation may reflect socioeconomic and other environmental factors., (Copyright 2001 S. Karger AG, Basel.)

A genetic heterogeneity analysis of 35 kindreds with adult-onset polycystic kidney disease (ADPKD) was carried out using the D16S85, D16S84, D16S125 and D16S94 loci that are closely linked to the PKD1 locus on chromosome 16. The results show that the likelihood of two ADPKD loci is 2,514.9 times greater than for a single locus (P < 0.0001). The maximum likelihood lod score is 27.38 under heterogeneity with PKD1 lying 4.9 cM proximal to D16S85 (in males). At least 3% of kindreds are unlinked to PKD1, since the 95% confidence limits of alpha, the proportion of families linked to PKD1, are 0.54-0.97. Only 2 out of 35 kindreds (5.7%) show statistically significant evidence of non-linkage to PKD1, with conditional probabilities of 0.987 and 0.993 that the disease locus is unlinked. This confirms the existence of a small subgroup of ADPKD kindreds that are unlinked to PKD1 and provides a firm basis for genetic counselling of this population on the basis of DNA probes.

Reproductive fitness of carriers of heterochromatic variants of the human karyotype was found to be normal. The method was based on a comparison between known carriers and known non-carriers from the same pedigree in respect of live births, generation time and survival of offspring to reproductive age. A subset of the data had been included in an earlier study in which reproductive fitness of carriers was found to be significantly reduced. Our analysis suggests that the result may have been fortuitous, since it was not supported by the additional data. There was no evidence of heterogeneity between carriers of different types of variant or of different sex. There were indications of increased fetal losses to carriers, but the number of spontaneous abortions was insufficient to produce a detectable effect on gross reproductive fitness.

In an attempt to resolve conflicting evidence from the literature concerning the existence of a paternal age effect in 46,X,i(Xq) Turner's syndrome, we have analysed data on all known cases ascertained in the main population centres of Scotland and on others ascertained in England, using population controls matched for year of birth. There was a significant (P = 0.02) increase of 2.3 years in the mean paternal age of the Scottish cases, and a smaller and non-significant increase in their mean maternal age. Logistic regression analysis confirmed that the primary association was with paternal, rather than maternal, age. For the English cases, however, there were small and non-significant decreases in their mean maternal and paternal ages. The differences between the two groups were also significant, but cannot be explained by any likely source of ascertainment bias. We therefore conclude that there is no evidence for a universal paternal age effect in this condition, but that at least one mechanism of origin, occurring with variable frequency, may be associated with increased paternal age. Using data from this and earlier published studies, we estimate the incidence of individuals with a 46,X,i(Xq) cell line to be between 3.3 and 13 per 10(5) female livebirths.

Data on 290 non-mosaic 47,XXY males have been analysed for possible associations with parental ages at birth, season of birth, sex ratio among sibs, and twinning. Comparison with matched population controls revealed a highly significant association with parental age, which was fully explained by dependence on maternal age and maternal age alone. The maternal age effect was determined with greater precision than in an earlier study of the same material, in which siblings were used as controls, and was estimated to result in an increased risk of between 5% and 10% per annum (p.a.). The estimated independent effect of paternal age, after fitting maternal age, was marginally (but not significantly) negative, and excluded an increased risk in excess of 3% p.a. Paternal age therefore appears to have little if any independent significance in the aetiology of 47,XXY. After correcting for seasonal variations in the population birth rate and smoothing, there was a peak of XXY births in March and a trough in November. Though not statistically significant, the pattern resembled that reported in previous studies, and was similar for both younger and older mothers. The twinning rate for both the XXYs and their sibs, and the sex ratio among the latter, were close to the corresponding population values.

Data on Turner Syndrome from four sources were analysed for possible associations with several aetiological factors. Two classes of liveborn propositae were included, those with a non-mosaic 45, X karyotype (XO) and those with an isochromosome of the long arm of the X (iso-X). The numbers were 288 and 84 respectively and constitute the largest series of such cases to be analysed to date. For the XO's, an analysis using the liveborn full sibs of propositae as controls (method of Carothers et al. 1978) confirmed earlier studies in finding no positive association with parental age or birth order, and even suggested a small negative association. There were no significant differences between the mean parental ages of those cases shown by Xg grouping to have received a maternal X chromosome and those of the remainder. Among the iso-X's there was an exceptionally high proportion (17.5%) of parents with an age difference (paternal-maternal) of 10 or more years, raising the possibility of a paternal age effect. This agrees with earlier studies but conflicts with the finding of a negligible tendency for affected individuals to be born later within their sibships. The apparent discrepancy may be due to the relative insensitivity of the latter method to small parental age effects in samples of this size. For the XO's there were no detectable seasonal variations in the month of birth, but for the iso-X's there was a significant excess of births in the first 6 months of the year. Reviewing the conflicting evidence from the literature on seasonal variations in chromosomal aberrations, we urge caution in interpreting these results. In agreement with earlier studies, the incidence of twins among both XO's and iso-X's was higher than the population average, but the numbers were too small for statistical significance. There was no evidence for any alteration in the sex ratio among the liveborn sibs of either class.

The use of Scottish public records to assist in the study of genetic disease is described. Four examples are given of situations in which such data can assist in the management of genetic disease. Some problems and limitations are discussed.

A family which segregates simultaneously for PGD, elliptocytosis, Rh, alphaFUC and PGM1 contains a recombinant suggesting that the loci lie in this order.