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J S Waye

Publications and source records attributed to J S Waye.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hb E/Hb LeporeHollandia in a family from Bangladesh.

We describe a family from Bangladesh in which three children are compound heterozygotes for Hb E (alpha 2 beta 2, beta 26Glu Lys) and Hb Lepore (delta-beta fusion gene). PCR amplification and direct nucleotide sequencing established that the fusion gene is Hb LeporeHollandia, with the cross-over localized to a 40 bp window between codon 22 and IVS-1 nt 16 of the delta- and beta-globin genes. This unusual combination of mutations is associated with a relatively mild clinical phenotype, with all three affected siblings having microcytic anemia of moderate severity without the need for transfusions.

Bangladesh↗
PubMed1994

Hb FM-Fort Ripley: confirmation of autosomal dominant inheritance and diagnosis by PCR and direct nucleotide sequencing.

We describe a normal neonate who presented at four days of age with asymptomatic cyanosis. There was no evidence of cardiac or pulmonary abnormality and an extended family history included 13 other affected family members with asymptomatic cyanosis lasting one to three months. Polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of the proband's G gamma chain gene revealed the mutation at codon 92 (CAC-->TAC) previously shown in haemoglobin FM-Fort Ripley (alpha 2 gamma G gamma 92 (F8) His-->Tyr). This is the first family with Hb FM-Fort Ripley reported so far. It demonstrates autosomal dominant inheritance of this condition and incomplete penetrance.

Amino Acid Sequence↗
PubMed1994

Allele frequency data for VNTR locus D17S79: identification of an internal HaeIII polymorphism in the black population.

D17S79 is one of several highly polymorphic VNTR loci commonly used to generate DNA profiles for forensic identity testing and parentage determination. In this study, we used Southern hybridization analysis of HaeIII-digested genomic DNA to compile D17S79 allele frequency databases for the Caucasian, Southeast Asian, East Indian, and Black populations of Southern Ontario. In our Black population sample, low-molecular-weight D17S79 alleles are relatively common and approximately 7% of the individuals have three-band hybridization patterns due to a HaeIII restriction site polymorphism within a common D17S79 allele. The internal HaeIII site generates an allele consisting of two HaeIII fragments of approximately 980 and 420 bp. The estimated frequency of this "split-allele" in our Black population is 0.035. Since this allele was not observed in the other population groups, the internal HaeIII polymorphism probably originated within the Black population. Although the existence of low-molecular-weight alleles and the internal HaeIII polymorphism could affect the interpretation of some VNTR patterns, they are of little or no forensic consequence to the frequencies assigned to VNTR profiles.

Alleles↗
PubMed1994

Identification of a novel beta O-thalassaemia mutation in a Greek family and subsequent prenatal diagnosis.

We present a case in which a Greek couple was considered not to be at risk of having children with homozygous beta-thalassaemia, an assessment based largely on the father's belief that he carried alpha-thalassaemia. After their first child was diagnosed with homozygous beta-thalassaemia, the case was re-assessed and both parents were shown to have the haematological profile of beta-thalassaemia trait. Screening for the common Mediterranean mutations demonstrated that the mother carries the IVS-1 nt 110 G-->A beta(+)-thalassaemia mutation. Direct nucleotide sequencing of PCR-amplified DNA revealed that the father carries a novel beta O-thalassaemia mutation, frameshift codons 9/10 (+T). The couple's second pregnancy was terminated after prenatal testing revealed that the fetus had inherited both parental mutations. This case illustrates the need to confirm the carrier status of individuals prior to assessing their genetic risks, and highlights the importance of being able to identify rare or novel beta-thalassaemia mutations.

Base Sequence↗
PubMed1994

Trinucleotide repeat polymorphism within the human antithrombin gene (AT3): allele frequency data for three population groups.

The fifth intron of the human antithrombin gene (AT3) of chromosome 1q23 contains a highly polymorphic short tandem repeat based on the trinucleotide repeat [ATT]. Alleles range in size from [ATT]5 to [ATT]18, and can be typed using the polymerase chain reaction. Here we report allele frequency population data for Caucasians, Blacks and Southeast Asians. Statistical analyses demonstrate consistency with Hardy-Weinberg equilibrium for all three databases, and that the allele frequencies of all three population groups are significantly different from each other. This locus reveals 76% to 87% heterozygosity and therefore may be useful for forensic identity testing and paternity determination.

Alleles↗
PubMed1994

Filipino beta-thalassemia due to a large deletion: identification of the deletion endpoints and polymerase chain reaction (PCR)-based diagnosis.

The gene frequency of beta-thalassemia among Filipinos is estimated to be 0.02, although little is known about the mutations involved. Recently, an extensive beta-thalassemia deletion was reported in several unrelated individuals of Filipino descent. The deletion begins approximately 4 kb upstream of the beta-globin gene, and extends 3' beyond the beta-globin gene. In this report, we identify the 5' and 3' deletion endpoints and present a polymerase chain reaction (PCR) strategy for rapid DNA diagnosis of the Filipino beta-thalassemia deletion.

Base Sequence↗
PubMed1994

Beta-thalassemia intermedia in a Lebanese child due to homozygosity for the -88 (C-->T) mutation.

We report a case of beta-thalassemia intermedia involving a 3-year-old male child of Lebanese descent. Molecular studies of the family showed that he is homozygous for the -88 (C-->T) beta (+)-thalassemia mutation. This mutation is the second most common cause of beta-thalassemia in Black populations, and has also been reported in Asian Indians. A review of Lebanese beta-thalassemia cases revealed considerable mutation heterogeneity and excess homozygosity due to consanguinity.

Adult↗
PubMed1994

Delta beta-thalassemia in an African-American: identification of the deletion endpoints and PCR-based diagnosis.

We describe an African-American child with beta-thalassemia intermedia. Molecular studies revealed that the proband is a compound heterozygote for the -29 (A-->G) beta (+)-thalassemia mutation and an extensive deletion involving the delta- and beta-globin genes. The proband's mother is a simple carrier of the deletion and exhibits the phenotype of delta beta-thalassemia rather than hereditary persistence of fetal hemoglobin. The deletion spans 11,767 bp, with the 5' deletion endpoint located 2,455 bp upstream of the delta-globin gene mRNA Cap site and the 3' endpoint located 441 bp downstream of the termination codon of the beta-globin gene. Based on this information, we have developed a polymerase chain reaction strategy for the rapid detection of this delta beta-thalassemia deletion.

Adult↗
PubMed1994

Anomalous migration of PCR products using nondenaturing polyacrylamide gel electrophoresis: the amelogenin sex-typing system.

Sex-typing of biological samples can be accomplished using the polymerase chain reaction (PCR) to amplify DNA sequences that are specific for the Y-chromosome. One such system is based on PCR amplification of the X-chromosome amelogenin gene and the amelogenin-like sequences located near the centromere of the Y-chromosome. The X and Y PCR products can be distinguished from each other on the basis of a 177 basepair (bp) insertion in the X relative to the Y. In this report, we demonstrate that the amelogenin PCR products migrate anomalously using non-denaturing polyacrylamide gel electrophoresis (ND-PAGE) as opposed to agarose gel electrophoresis or denaturing PAGE. These results may be relevant to the choice of electrophoretic system used to analyze highly polymorphic loci for individual identification.

Amelogenin↗
PubMed1993

Immunocytological test to detect adult carriers of (--SEA/) deletional alpha-thalassaemia.

The gene frequency for (--SEA/) deletional alpha-thalassaemia is high in Southeast Asian populations. We report a simple immunocytological test that is highly sensitive and specific for the detection of adult carriers of the (--SEA/) deletion. We prospectively studied 206 consecutive adult blood samples. All 41 with the (--SEA/) deletion had a positive test; all but 1 of the 165 non-carriers were negative. This test, whose major requirement is a fluorescence microscope, should be useful to identify couples at risk of conceiving fetuses with homozygous alpha-thalassaemia.

Adult↗
PubMed1993

Expression of embryonic zeta-globin and epsilon-globin chains in a 10-year-old girl with congenital anemia.

A 10-year-old Danish girl with congenital anemia is described. At birth, she had severe anemia and erythroblastosis and was transfused a number of times during the first year. The need for transfusions has since declined steadily. Her reticulocyte counts varied between 2% and 15%, and her bone marrow aspirate showed some dyserythropoietic features. Her hemoglobin F level was consistently elevated, up to as much as 41%. Her erythrocytes had a normal level of I antigen but an undetectable level of i antigen. Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes. These findings may represent the manifestations of a new variant of congenital anemia.

Adolescent↗
PubMed1993

Complications in the genotypic molecular diagnosis of pseudo arylsulfatase A deficiency.

Metachromatic leukodystrophy (MLD) is a severe neurodegenerative disease associated with deficient arylsulfatase A activity. Biochemical confirmation of this disorder has been complicated by a clinically normal but enzymatically deficient variant, pseudo arylsulfatase-A deficiency (PD). The PD mutation is associated with two A-->G transitions in the arylsulfatase A gene. They can be detected simultaneously with a recently developed 3'-mismatch polymerase chain reaction, hence providing a rapid method for genotypic identification and resolving ambiguities of carrier identification based solely on enzyme analyses. However, we now report further genotypic complexities in the molecular diagnosis of PD due to the occurrence of another variant in which only one of the two A-->G mutations of the PD allele was present. This variant confers reduced but readily detectable enzyme activity and behaves as a silent allele in the 3'-mismatch polymerase chain reaction, thus leading to conflicting and erroneous genotype assignments in a family in which both variants and MLD co-exist. The inconsistency was resolved after pedigree validation and further molecular analyses in which the two A-->G mutations were assayed separately with allele-specific oligonucleotides. Because arylsulfatase A analysis is one of the most commonly requested lysosomal enzyme assays and the PD mutant allele frequency is high in the general population, complexities as described in this family may be a recurrent problem that can be solved only with combined enzymatic and detailed molecular analyses.

Adult↗
PubMed1993

Identification of two novel beta zero-thalassemia mutations in a Filipino family: frameshift codon 67 (-TG) and a beta-globin gene deletion.

The frequency of beta-thalassemia alleles among Filipinos is estimated to be 0.02, although little is known about the actual mutations represented in this population. Here, we describe a Filipino family in which a child has severe beta-thalassemia major. Molecular studies of the family revealed that the proband is a compound heterozygote for two previously unreported beta zero-thalassemia alleles: a frameshift mutation (-TG) at codon 67 and a deletion of the entire beta-globin gene. The 5' endpoint of this novel deletion is located approximately 3.9 kb to approximately 4.3 kb upstream of beta-globin gene, and the deletion extends 3' beyond the beta-globin gene for an undetermined distance. The occurrence of two novel beta-thalassemia alleles in a single family suggests that the Filipino population may have a unique spectrum of beta-thalassemia alleles.

Alleles↗
PubMed1993

B-cell lymphoma of recipient origin 9 years after allogeneic bone marrow transplantation for T-cell acute lymphoblastic leukaemia.

A 25-year-old woman developed an immunoblastic lymphoma 9 years after HLA-identical allogeneic bone marrow transplantation for T-cell acute lymphoblastic leukaemia in second remission. The B-cell origin of the second malignancy was confirmed by gene rearrangement studies. Despite continued donor engraftment, two separate genotypic analyses identified the lymphoma to be of recipient origin. This is the longest latency of a post-transplant recipient lymphoma yet reported and illustrates that recipient B-cells may survive the transplant conditioning regimen and undergo malignant transformation in the presence of donor haemopoiesis.

Adolescent↗
PubMed1993

Nonrandom localization of recombination events in human alpha satellite repeat unit variants: implications for higher-order structural characteristics within centromeric heterochromatin.

Tandemly repeated DNA families appear to undergo concerted evolution, such that repeat units within a species have a higher degree of sequence similarity than repeat units from even closely related species. While intraspecies homogenization of repeat units can be explained satisfactorily by repeated rounds of genetic exchange processes such as unequal crossing over and/or gene conversion, the parameters controlling these processes remain largely unknown. Alpha satellite DNA is a noncoding tandemly repeated DNA family found at the centromeres of all human and primate chromosomes. We have used sequence analysis to investigate the molecular basis of 13 variant alpha satellite repeat units, allowing comparison of multiple independent recombination events in closely related DNA sequences. The distribution of these events within the 171-bp monomer is nonrandom and clusters in a distinct 20- to 25-bp region, suggesting possible effects of primary sequence and/or chromatin structure. The position of these recombination events may be associated with the location within the higher-order repeat unit of the binding site for the centromere-specific protein CENP-B. These studies have implications for the molecular nature of genetic recombination, mechanisms of concerted evolution, and higher-order structure of centromeric heterochromatin.

Base Sequence↗
PubMed1993

Carrier detection and prenatal diagnosis of hemoglobinopathies in Ontario.

The province of Ontario has a total population of approximately 10 million people, with approximately 20% being of African, Southeast Asian, East Indian, Mediterranean, or Middle Eastern ancestry in whom the gene frequency for hemoglobinopathies is relatively high. In 1989, the Ontario Ministry of Health funded the establishment of the Provincial Hemoglobinopathy DNA Diagnostic Laboratory located at the McMaster University Medical Centre in Hamilton, Ontario. The Laboratory provides DNA analysis to identify the globin gene mutations in carriers and affected individuals, and performs prenatal diagnosis for severe hemoglobinopathies. Annually, more than 400 patient samples are referred to the Laboratory for investigation, of which 25-35 are fetal samples from pregnancies at risk for either homozygous alpha-thalassemia, beta-thalassemia major, or sickling disorders. We have detected more than 70 different globin gene mutations, including several mutations not previously reported in the literature. Here we present examples of the approaches used to detect globin gene mutations in a heterogeneous "at risk" population such as in Ontario, and discuss the impact of this service on patient care, genetic counselling, and the incidence of severe hemoglobinopathies in Ontario.

DNA↗