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S L Sherman

Publications and source records attributed to S L Sherman.

At least 91 records · Page 5Linked to original sources
PubMed1986

A strategy for multipoint ordering: example of the 11p markers.

The complete likelihood analysis is required to obtain the evidence for the gene order. Since the number of candidate orders increases rapidly with the number of loci and the complete analysis requires considerable computer time, a method for rapidly screening order is required. To this end, we used the program MAP83 for the initial investigation of order. This method provided a subset of orders to be further investigated by the complete likelihood method. We used PAP for these subsequent analyses. The advantage of algorithms such as MAP83 is that the basic unit of analysis is the set of pairwise LOD scores which are routinely calculated at the beginning of a linkage analysis. However, the magnitude of the log likelihood differences between orders can only be suggestive for two reasons. First, the usual assumptions for MAP83 regarding independence of the recombination fraction estimate are not met by these data and, therefore, no attempt can be made to interpret the log likelihood differences statistically. Secondly, pairwise information precludes identifying the specific inheritance pattern of each gamete, thus the information content of obligatory multiple recombinants is lost. For example, the order HBBC-ADJ-HRAS1-INS requires five double recombinants for the Utah data while the order HBBC-ADJ-INS- HRAS1 does not require any (White et al, 1985). The support for the former order over the latter is a log likelihood difference of 3.73 for the complete likelihood analysis when the HBBC locus is ignored.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Mapping↗
PubMed1986

Genetic analysis workshop IV: summary for coeliac disease.

Two groups analyzed the pedigrees with CD using two different approaches. Louis et al (1986, referred to as Louis) first analyzed the haplotype information to determine which HLA antigens were significantly associated with CD. Subsequently, they used the antigen genotype frequencies among patients (AGFAP) method (Thomson, 1983) to determine the mode of inheritance of the HLA-linked susceptibility gene and to determine the number of possible alleles at that locus. Sherman et al (1986, referred to as Sherman) used the method of MacLean et al (1984) which combines segregation, linkage and association information to define the susceptibility locus. The model assumed that the phenotype of an individual was the result of independent contributions of a genetic component and random environment. The genetic contribution was partitioned into two components: the effect due to the major gene which is linked to HLA and the effect due to the modifier which is not linked to HLA. The modifier was included to absorb additional family resemblance such as polygenes or environmental factors. Both groups analyzed the Liverpool data of Ellis et al (1981) separately. The data of Tiwari et al (1984) was analyzed as one data set by Sherman whereas Louis used a subset of these data, first analyzing the 30 BLG French families and subsequently combining the 13 probands from the BET French families. Both groups used similar association information to define the segregation of the HLA-linked susceptibility gene. Louis found that the haplotype A1-B8 was significantly associated with CD in the Liverpool data and that the DR3 and DR7 specificities were significantly associated in the French data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Segregation analysis of rare autosomal fragile sites.

Segregation analyses were performed on pedigrees with rare autosomal fragile sites. The results of the analysis of pedigrees with folate sensitive fragile sites, including 2q1, 6p23, 7p11, 8q22, 9q32, 10q23, 11q13, 11q23, 12q13, 16p12, and 20p11, suggested that expression of the gene depended on the carrier parent: it was only 50% penetrant when transmitted by a carrier father, but fully penetrant when transmitted by a carrier mother. Pedigrees with the bromodeoxyuridine (BrdU) fragile site, fra(10)(q25), showed the same trend but the results were not statistically significant. In addition, 38 of the 44 probands with folate sensitive or BrdU-sensitive fragile sites received the gene from their carrier mother and only six received it from their father. In contrast, the analysis of pedigrees with the distamycin A-inducible site, fra(16)(q22), gave the results expected for a simple codominant trait with complete penetrance. Probands with this fragile site received the gene equally from mothers or fathers. The genetic implications of these results are discussed.

Bromodeoxyuridine↗
PubMed1986

Segregation analysis of balanced pericentric inversions in pedigree data.

The results of the recent European collaborative prenatal study suggested a segregation distortion of balanced pericentric inversions from carrier fathers but not carrier mothers (Boué & Gallano 1984). In an attempt to confirm these unexpected results, we examined 216 pedigrees with balanced pericentric inversions collected from three centers and from the literature. We were unable to detect any significant deviation from the expected 1:1 segregation of balanced pericentric inversions to normal karyotypes among the offspring of either carrier parent. To clarify the discrepancy between the studies, we reanalyzed the data from the prenatal study using all karyotyped individuals and, assuming conventional ascertainment rules, found a normal segregation pattern. We conclude that balanced pericentric inversions segregate normally in both males and females and that some retrospectively selected pedigrees were included as prospective in the prenatal study and this misclassification caused the apparent segregation distortion from carrier fathers.

Chromosome Inversion↗
PubMed1985

Further segregation analysis of the fragile X syndrome with special reference to transmitting males.

A new series of 96 pedigrees with the fra(X) syndrome was analysed using complex segregation analysis with pointers, defining affection as any degree of mental impairment. These families were found to exhibit the same segregation pattern as the first series of 110 pedigrees (Sherman et al. 1984). The best estimate for penetrance of mental impairment in males was 79% and in females was 35% for the combined data. Again, there was little evidence for sporadic cases among affected males. Many more intellectually normal transmitting males have been observed since the existence of such males and the concomitant need to investigate the paternal side of pedigrees was recognized. On further investigation of all 206 pedigrees from the old and new data sets, the sibships of nonexpressing males appeared to be different from those of expressing males. Our analysis, using mental impairment as the phenotype, suggested that obligate carrier mothers and daughters of intellectually normal transmitting males are rarely, if ever, mentally impaired and that the sibs of transmitting males are much less likely to be retarded than the sibs of mentally impaired males. Though mothers and daughters of transmitting males are similar in phenotype, the expression of the gene in their offspring appears to be different: the penetrance of mental impairment is higher in offspring of intellectually normal daughters of transmitting males than in offspring of intellectually normal mothers of transmitting males. The implications of these observations for genetic counseling and for genetic models of the fra(X) syndrome are discussed.

Female↗
PubMed1984

Genetic Analysis Workshop II: combined segregation, linkage, and association analysis.

A combined segregation, linkage, and association analysis using the program COMBIN was performed on the simulated pedigree data prepared for the Second Genetic Analysis Workshop. The model used in COMBIN is described and the presented results illustrate its effectiveness in the analysis of such data. Linkage analysis was performed and maps for each linkage group are presented.

Adult↗
PubMed1984

The marker (X) syndrome: a cytogenetic and genetic analysis.

The results of a cytogenetic and segregation analysis of 110 pedigrees of the mar (X) syndrome are reported. The cytogenetic study indicated an inverse relationship between IQ and the mar(X) frequency in females but not in males. A small but significant effect of age on mar(X) frequency was observed in both males and females, but in females it was restricted to those of normal intelligence, retarded females showing no significant effect. Classical segregation analysis was performed using the program SEGRAN, analysing sexes separately. A 20% deficit of affected males was observed, the most plausible explanation for the majority of these cases being incomplete penetrance. Since this was an unexpected result, the data were scrutinized for possible biases; however, correction of these had little effect on the estimate. The penetrance of mental impairment in carrier females was estimated to be 30% and of mental impairment and/or mar(X) expression to be 56%. Thus 44% of carriers cannot be detected with our definition of affection. No evidence for sporadic cases among affected males was found. Complex segregation analysis was performed using the sex-linked version of POINTER, analysing sexes together. This was done in order to test the results from classical segregation analysis, to test for family resemblance and to estimate mutation rates. It was confirmed that there was a 20% deficit of affected males, that penetrance of mental impairment in females was approximately 30% and that there was no evidence for sporadic males. Thus all males with the gene appear to have received it from their carrier mothers and all mutations must occur in sperm. The mutation rate in sperm was estimated to be as high as 7.2 X 10(-4), implying that over one-half of random carrier females are fresh mutants. Our results have important implications for genetic counseling as they imply that all mothers of isolated affected males are carriers, that normal brothers of affected males have a 17% chance of carrying the gene and transmitting it to all their daughters, and that normal sisters of affected males have, at most, a 30% chance of being carriers. Since there are biases in the data due to the testing of particular individuals, these probabilities must be considered approximations until they are independently confirmed.

Adolescent↗
PubMed1984

A revised map of chromosome 1.

The genetic map of chromosome 1 reported by Keats, Morton & Rao (1981) has been updated using recent recombination data and regional assignments from the Galton Laboratory (King, 1982a) and from the current literature. A maximum likelihood mapping technique using pairwise recombination data without a chiasma map was developed, based on the principles of Rao et al. (1979) and Keats et al. (1981). The development of this new method was found to be necessary when inconsistencies were encountered using a method which combines recombination data and physical data through the chiasma map. These inconsistencies could be due to appreciable chiasma movement, incorrect physical assignments or technical and biological variation in lod scores.

Chromosome Mapping↗
PubMedDate not supplied

Investigation of the twinning rate in families with the fragile X syndrome.

An excess of twins in families with the Martin-Bell or fra(X) syndrome was noted previously in one family study [Fryns, 1986]. We tried to confirm this observation in a second large sample of families from a different population. We calculated the number of twin births among the total number of live births of known obligate carriers found in fra(X) families ascertained in New South Wales, Australia. We only included births of known sex and excluded triplets. There were 5 male pairs, 3 female pairs and 9 unlike sex pairs of twins born among 752 live births. Thus the twining rate was 1/44 per live birth. We compared this rate to that found in two different types of individuals: 1) the rate of 1/96 which was obtained from the 1985 vital statistics for New South Wales, and 2) the rate 1/75 obtained from a sample of live births of obligate carriers with hemophilia A. The increase in twinning among heterozygotes with the fra(X) was highly significant when compared to the census data (p less than 0.001). However, it was not significantly different from that in the hemophilia data (p less than 0.05) which were collected in the same way as in the fra(X) families.

Epidemiologic Methods↗
PubMedDate not supplied

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.

Female↗
PubMedDate not supplied

Collaborative prospective study of the fragile X syndrome: request for participation.

A collaborative prospective study of the fragile X syndrome (fra[X]) has been initiated to refine the estimates of the recurrence risks based on the phenotype of the mother and the family history of the syndrome. The basic unit of data consists of the description of the pregnancy outcome of women known to carry the fra(X) mutation or who are mothers of a fra(X)-positive son. Pregnancy outcome includes both prenatal diagnoses and live-borns. The prospective nature of the data eliminates problems of ascertainment and thereby provides more accurate estimates. The specific aims of the study are both clinically and research oriented: 1) refine the estimates of recurrent risks based on the phenotype of the mother and on family history for use in genetic counseling; 2) determine if recurrence risks depend on the phenotype of the carrier parent; 3) determine if a proportion of affected individuals is due to new mutations; and 4) determine the reproductive fitness of fra(X) carriers. This paper describes the rationale behind this study, the data to be collected, and the sample sizes necessary to test hypotheses. Most importantly, participation in this collaborative study is requested from all professionals who work with the fra(X) syndrome.

Data Collection↗