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S P Daiger

Publications and source records attributed to S P Daiger.

At least 55 records · Page 3Linked to original sources
PubMed1992

Human chromosome 8 linkage map based on short tandem repeat polymorphisms: effect of genotyping errors.

A linkage map consisting of 21 dinucleotide repeat polymorphisms, 1 tetranucleotide repeat polymorphism, and 3 RFLPs was constructed for human chromosome 8. The map spanned most of the chromosome length from near pter to q23-q24 on the distal portion of the long arm. The total 186 cM length of the female map was over two times the 84 cM length of the male map. Cytogenetic mapping of the polymorphisms using a panel of hybrids containing rearranged chromosomes was completely consistent with the linkage map. Special effort was made to remove as many genotyping errors, including parental phase errors, as possible. Removal of errors, in agreement with recent theoretical predictions, led to reduction of the total length of the sex-equal map by 10% from 145 to 130 cM.

Alleles↗
PubMed1992

Apparent heterozygote deficiencies observed in DNA typing data and their implications in forensic applications.

Restriction fragment length polymorphisms (RFLP) analysis using the Southern blot technique can be used to recognize copy number variation of variable number of tandem repeats (VNTR) of conserved core sequences at several regions of the human genome. This new class of polymorphisms reveals a high degree of genetic variation, useful for individual identification purposes. Criticisms against forensic applications of such DNA typing data include the limitation of employing Hardy-Weinberg expectation of genotype frequencies, since several surveys indicate apparent deficiency of heterozygosity (or excess homozygosity) in comparison with Hardy-Weinberg expectations. This research postulates an alternative explanation of deficiency of apparent heterozygosity which is caused by the inability to detect extremely small-sized alleles (called 'non-detectable' alleles) due to the sensitivity of Southern gel electrophoresis. We show that the presence of 'non-detectable' alleles can produce pseudo-homozygosity and their frequencies can be predicted from the observed proportional heterozygote deficiency. Furthermore, in the covert presence of such 'non-detectable' alleles, we show that the gene-count method provides over-estimates of allele frequencies in the sample population, and hence the Hardy-Weinberg predictions of genotype frequencies avoid wrongful bias against suspects in forensic applications of DNA typing data. Applications of this theory to population data on six VNTR loci in US Caucasians and US Blacks suggest that the presence of 'non-detectable' alleles could be the major cause of apparent heterozygote deficiency, and the current approaches of predicting the population frequency of specific DNA phenotypes are practically free of the possible wrongful bias in courtroom applications of DNA typing data.

Alleles↗
PubMed1992

Evidence for genetic heterogeneity in tuberous sclerosis: one locus on chromosome 9 and at least one locus elsewhere.

Linkage of tuberous sclerosis complex (TSC), an autosomal dominant disorder, to markers on chromosome 9 was reported first in 1987. This assignment was confirmed by an international collaborative study that suggested more than one locus may be responsible for the phenotype. We studied 14 multigenerational TSC families (13 previously unreported) with markers for nine loci in the linked region of chromosome 9q32-q34. Our results confirm the previous reports that the genetic locus in one-third to one-half of families maps to chromosome 9. Comparison of clinical findings in the chromosome 9-linked families with those in the chromosome 9-unlinked families reveals only a higher incidence of ungual fibromata in the chromosome 9-linked families.

Alleles↗
PubMed1992

Linkage between Rh blood group and autosomal dominant retinitis pigmentosa in ten Chinese families.

Since Fei et al reported a tentative linkage between ADRP and the Rhesus(Rh) blood group in the unrelated Chinese families in 1987, additional individuals of these ADRP families have been typed for Rh. Further linkage analysis with the LIPED Program on the Rh data of the ten ADRP families showed a maximum summed LOD score of 2.01 at theta = 0.12, which is a further suggestion of linkage between ADRP and Rh. However, genetic heterogeneity certainly exists in these families. It is our presumption that ADRP in those families, which do not exhibit linkage to 3q markers, may map to the short arm of chromosome 1.

Female↗
PubMed1991

Autosomal dominant sectoral retinitis pigmentosa. Two families with transversion mutation in codon 23 of rhodopsin.

A cytosine-to-adenine transversion in codon 23 of rhodopsin, the rod visual pigment gene, was reported recently by Dryja et al in 17 of 148 unrelated patients with autosomal dominant retinitis pigmentosa, but the clinical findings associated with this deletion have not been reported in detail. In screening our patients with autosomal dominant retinitis pigmentosa for the codon 23 transversion, we found positive results in four affected individuals from two families with sectoral retinitis pigmentosa, while 12 patients with sectoral retinitis pigmentosa from different families had negative results, suggesting that other gene sites or locations may give this same phenotypic change. From our patients' history of light exposure and the location of degeneration in the retina, we hypothesize that light phototoxicity may be playing an expressive role in this point mutation of the rhodopsin gene. This is the first report in which a type of retinitis pigmentosa has been associated with a specific molecular gene defect, although the actual pathophysiologic mechanism currently is unknown.

Adult↗
PubMed1991

Linkage mapping of autosomal dominant retinitis pigmentosa (RP1) to the pericentric region of human chromosome 8.

Linkage mapping in a large, seven-generation family with type 2 autosomal dominant retinitis pigmentosa (ADRP) demonstrates linkage between the disease locus (RP1) and DNA markers on the short arm of human chromosome 8. Five markers were most informative for mapping ADRP in this family using two-point linkage analysis. The markers, their maximum lod scores, and recombination distances were ANK1 (ankyrin)--2.0 at 16%; D8S5 (TL11)--5.3 at 17%; D8S87 [a(CA)n repeat]--7.2 at 14%; LPL (lipoprotein lipase)--1.5 at 26%; and PLAT (plasminigen activator, tissue)--10.6 at 7%. Multipoint linkage analysis, using a simplified pedigree structure for the family (which contains 192 individuals and two inbreeding loops), gave a maximum lod score of 12.2 for RP1 at a distance 8.1 cM proximal to PLAT in the pericentric region of the chromosome. Based on linkage data from the CEPH (Paris) reference families and physical mapping information from a somatic cell hybrid panel of chromosome 8 fragments, the most likely order for four of these five loci and the diseases locus is 8pter-LPL-D8S5-D8S87-PLAT-RP1. (The precise location of ANK1 relative to PLAT in this map is not established). The most likely location for RP1 is in the pericentric region of the chromosome. Recently, several families with ADRP with tight linkage to the rhodopsin locus at 3q21-q24 were reported and a number of specific rhodopsin mutations in families with ADRP have since been reported. In other ADRP families, including the one in this study, linkage to rhodopsin has been excluded. Thus mutations at two different loci, at least, have been shown to cause ADRP. There is no remarkable clinical disparity in the expression of disease caused by these different loci.

Base Sequence↗
PubMed1991

Cleft lip and palate: no evidence of linkage to transforming growth factor alpha.

Recently, an association of a specific transforming growth factor alpha (TGFA) haplotype has been reported to occur in patients with nonsyndromic cleft lip and palate (CLP) who had a positive family history of the disorder. We tested linkage of CLP to TGFA in 12 multiplex families with clefting. TGFA haplotypes were constructed on the basis of three polymorphic restriction sites. No haplotype was associated with CLP, and discordant inheritance of TGFA haplotypes was observed in a single informative family. The log odds (LOD) score was -2.1 at theta = .05. These findings indicate that CLP and TGFA are not tightly linked in these families.

Alleles↗
PubMed1991

DNA fingerprinting.

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DNA Fingerprinting↗
PubMed1991

Polymorphisms at VNTR loci suggest homogeneity of the white population of Utah.

Apparent departure from equilibrium of genetic parameters measured for multiallelic single-locus markers such as VNTR (variable number of tandem repeat) loci has been suggested as evidence of underlying heterogeneity of the tested population. Using allele frequency distributions at eight VNTR loci from the white population of Utah, we show that the observed number of alleles and the gene diversity at each locus are congruent according to expectations of the neutral mutation model. This demonstrates the genetic homogeneity of the white population of Utah with reference to the allele (total and rare) frequency distribution at eight VNTR loci. The importance of such procedures is discussed in the context of using VNTR polymorphism data for forensic and medicolegal applications. Recommendations for reporting population data for hypervariable loci are also made to aid potential users in conducting similar analyses.

Gene Frequency↗
PubMed1990

Further evidence of exclusion of linkage between type II autosomal dominant retinitis pigmentosa (ADRP) and D3S47 on 3q.

Linkage of the anonymous DNA marker D3S47 (CRI-C17) and autosomal dominant retinitis pigmentosa (ADRP) was tested in a large, extended family with type II (late onset) ADRP. D3S47 has been shown previously to be tightly linked to the RP locus in one family with type I (early onset) ADRP (McWilliams et al., 1989, Genomics 5: 619-622). Linkage between ADRP type II and D3S47 has recently been excluded in a single family (Ingelhearn et al., 1990, Genomics 6: 168-173). Results of our linkage analysis clearly establish that type II ADRP in our family is unlinked to D3S47. These findings support the hypothesis that type II ADRP is genetically distinct from type I ADRP.

Chromosomes, Human, Pair 3↗
PubMed1989

Multilocus linkage analysis with the human argininosuccinate synthetase gene.

We have identified three restriction fragment length polymorphisms (RFLPs) from within the argininosuccinate synthetase (ASS) gene which maps to human chromosome 9q34-qter. Although RFLPs at pseudogene loci are detected by the cDNA, these are the first polymorphisms reported at the ASS locus. The three RFLPs are in linkage equilibrium with each other, and haplotypes for the ASS locus are highly informative. Two-locus recombination estimates between ASS and seven other 9q markers indicated that ASS is closest to the ABO blood group with a recombination fraction of 0.04 (0.005-0.11). A multilocus lod score analysis with these seven 9q markers indicated that ASS maps between ABL and MCT136 close to ABO, but it is uncertain if ASS is centromeric or telomeric to ABO.

Alleles↗
PubMed1989

Exclusion of Usher syndrome gene from much of chromosome 4.

Usher syndrome is an autosomal recessive disease characterized by dual sensory impairments; affected individuals are born with a sensorineural hearing loss and ultimately lose their sight as retinitis pigmentosa develops. Conventional protein markers previously tested in a Louisiana Acadian kindred suggested tentative linkage to vitamin D-binding protein on chromosome 4. DNA linkage studies do not confirm this linkage relationship and exclude much of chromosome 4 as the site of the Usher syndrome gene in these families.

Blindness↗
PubMed1989

Linkage analysis of human chromosome 4: exclusion of autosomal dominant retinitis pigmentosa (ADRP) and detection of new linkage groups.

As part of our ongoing linkage studies of degenerative retinal diseases, we tested seven DNA markers and two classical genetic markers from chromosome 4 in two extended families with autosomal dominant retinitis pigmentosa (ADRP). Our goals were (1) to detect or exclude linkage of ADRP to markers spanning most of chromosome 4 and (2) to contribute useful new information regarding the linkage map of this chromosome. Our results exclude linkage of ADRP from more than 82% of chromosome 4. We detected four new linkage relationships: loose linkage of K082 (D4S10) and G1E5 (D4S21) at a distance of 21 cM; loose linkage of 4F2 (D4S18) and GC protein at a distance of 19 cM; tight linkage (i.e., no recombinants) between B3D (D4S44), B5A (D4S40), and the MNS blood group; and tight linkage between 4F2 and GDS5 (D4S23). These data, combined with previously reported data, exclude ADRP from approximately 35% of the human genome.

Adolescent↗
PubMed1989

Assignment of autosomal dominant spinocerebellar ataxia (SCA1) centromeric to the HLA region on the short arm of chromosome 6, using multilocus linkage analysis.

A 7-generation kindred with the HLA-linked form of spinocerebellar ataxia (SCA1) was studied to determine whether the SCA1 gene maps centromeric or telomeric to the HLA loci. The DNA markers flanking the HLA-(A-B) region were used for polymorphism studies and multilocus linkage analysis. These two markers are the cDNA for the beta-subunit of HLA-DP, which is centromeric to HLA-(A-B), and the cDNA for coagulation factor XIIIa (F13A), which is telomeric to HLA-(A-B). Haplotypes were constructed using multiple polymorphisms for these two DNA markers, and pairwise linkage analysis revealed a maximum lod score of 2.18 for SCA1 versus HLA-DP at a recombination fraction of .05 and a maximum lod score of 0 for SCA1 versus F13A at a recombination fraction of .50. A possible crossover between HLA-(A-B) and HLA-DP was identified, but lack of samples from key individuals hampered the analysis. To clarify the phase and improve the analysis, the two chromosomes 6 for the crossover individual were separated in somatic cell hybrids. The results strongly favored the probability that the crossover occurred between HLA-(A-B-DR) and HLA-DP with SCA1 segregating with HLA-DP, consistent with a location centromeric to HLA-(A-B). Multilocus linkage analysis was used to evaluate further the location of SCA1 relative to F13A, HLA-(A-B), and HLA-DP; the results indicated that the SCA1 gene locus is centromeric to HLA-DP with odds of 46:1 favoring this most likely location over the second most likely location, i.e., telomeric to HLA-(A-B) between the HLA complex and F13A.

Animals↗