Search PubMed⌕ Search

Biomedical subjects

B N White

Publications and source records attributed to B N White.

At least 19 recordsLinked to original sources
PubMed2003

Association of autism severity with a monoamine oxidase A functional polymorphism.

A functional polymorphism (the upstream variable-number tandem repeat region, or uVNTR) in the monoamine oxidase A (MAOA) promoter region has been reported to be associated with behavioral abnormalities as well as increased serotonergic responsivity. We examined the relation between MAOA-uVNTR alleles and the phenotypic expression of autism in 41 males younger than 12.6 years of age. Children with the low-activity MAOA allele had both lower intelligence quotients (IQ) and more severe autistic behavior than children with the high-activity allele. In follow-up testing of 34 of the males at the 1-year time-point, those with the low-activity allele showed a worsening in IQ but no change in the severity of their autistic behavior. We conclude that functional MAOA-uVNTR alleles may act as a genetic modifier of the severity of autism in males.

Activities of Daily Living↗
PubMed2002

Evaluating the effects of historic bottleneck events: an assessment of microsatellite variability in the endangered, North Atlantic right whale.

Commercial exploitation reduced the North Atlantic right whale (Eubalaena glacialis) population from c. 12,000 in the 11th century to around 300 by the 21st century. We examine the effect of this population decline on levels of genetic variation at 16 microsatellite loci and contrast levels of variability to that in a closely related species (E. australis). Of the 13 loci developed from the E. glacialis genome, 100% were polymorphic in E. australis. In contrast, nine loci were polymorphic in E. glacialis and four were fixed. Both allelic diversity (A) and heterozygosity (H) were significantly lower in E. glacialis than E. australis (A = 3.2 +/- 2.6 vs. A= 6.9 +/- 3.3, P < 0.001; H= 0.31 +/- 0.25 vs. H= 0.72 +/- 0.23, P < 0.001, respectively). Bottleneck anlayses indicate that the population is in mutation-drift equilibrium and that a genetic bottleneck did not occur during the most recent decline (18th-20th centuries). Nevertheless, low frequency alleles are relatively uncommon in E. glacialis, suggesting that genetic variability has been reduced in this population. Possible origins of low genetic variability are discussed, including the slow but continual erosion of alleles during the 800-year period of decline.

Alleles↗
PubMed2002

Synaesthesia: a case study of discordant monozygotic twins.

We describe a study of 11-year-old twin sisters who are physically identical in appearance but who have considerably different conscious experiences. One twin appears to be a synaesthete in that she states that she has specific colour experiences (i.e. photisms) whenever she views, hears or thinks of digits. The other twin does not report such conscious experiences when viewing, hearing or thinking about digits. A genotypic analysis using eight microsatellite loci plus the gender of the twins and their parents confirmed that the twins are monozygotic. A phenotypic analysis using a modification of the Stroop task confirmed that only one twin is a synaesthete. We suggest that the discordance in synaesthesia may be due to either an epigenetic event, X chromosome inactivation, or a mutation of a synaesthesia gene.

Child↗
PubMed2001

Genetically determined low maternal serum dopamine beta-hydroxylase levels and the etiology of autism spectrum disorders.

Autism, a neurodevelopmental disability characterized by repetitive stereopathies and deficits in reciprocal social interaction and communication, has a strong genetic basis. Since previous findings showed that some families with autistic children have a low level of serum dopamine beta-hydroxylase (DbetaH), which catalyzes the conversion of dopamine to norepinephrine, we examined the DBH gene as a candidate locus in families with two or more children with autism spectrum disorder using the affected sib-pair method. DBH alleles are defined by a polymorphic AC repeat and the presence/absence (DBH+/DBH-) of a 19-bp sequence 118 bp downstream in the 5' flanking region of the gene. There was no increased concordance for DBH alleles in affected siblings, but the mothers had a higher frequency of alleles containing the 19-bp deletion (DBH-), compared to an ethnically similar Canadian comparison group (chi(2) = 4.20, df = 1, P = 0.02 for all multiplex mothers; chi(2) = 4.71, df = 1, P < 0.02 for mothers with only affected sons). Although the odds ratios suggested only a moderate relevance for the DBH- allele as a risk allele, the attributable risk was high (42%), indicating that this allele is an important factor in determining the risk for having a child with autism. DBH genotypes also differed significantly among mothers and controls, with 37% of mothers with two affected sons having two DBH- alleles, compared to 19% of controls (chi(2) = 5.81, df = 2, P = 0.03). DbetaH enzyme activity was lower in mothers of autistic children than in controls (mean was 23.20 +/- 15.35 iU/liter for mothers vs. 33.14 +/- 21.39 iU/liter for controls; t = - 1.749, df = 46, P = 0.044). The DBH- allele was associated with lower mean serum DbetaH enzyme activity (nondeletion homozygotes: 41.02 +/- 24.34 iU/liter; heterozygotes: 32.07 +/- 18.10 iU/liter; and deletion homozygotes: 22.31 +/- 13.48 iU/liter; F = 5.217, df = 2, P = 0.007) in a pooled sample of mothers and controls. Taken together, these findings suggest that lowered maternal serum DbetaH activity results in a suboptimal uterine environment (decreased norepinephrine relative to dopamine), which, in conjunction with genotypic susceptibility of the fetus, results in autism spectrum disorder in some families.

Alleles↗
PubMed2001

Application of DNA markers to identify the individual-specific hosts of tsetse feeding on cattle.

Primer sets for five different ungulate loci were used to obtain individual microsatellite DNA profiles for 29 Mashona cattle from a herd in Zimbabwe. There were 3-13 alleles for each locus and, using the entire suite of five loci, each animal within the herd, including closely related individuals, could be unequivocally distinguished. Wild-caught Glossina pallidipes Austen (Diptera: Glossinidae) were fed on specific cattle and the bloodmeal was profiled 0.5-72 h after feeding. The individual specific sources of the bloodmeals, including mixe meals produced by allowing tsetse to feed on two different cattle, were reliabl identified up to 24 h after feeding. The technique was used in field studies of hos selection by G. pallidipes and G. morsitans morsitans Westwood (Diptera Glossinidae) attracted to pairs of cattle. When the pair comprised an adult and a calf, 100% of meals were from the adult. For some pairs of adult cattle, tsetse were biased significantly towards feeding on one animal, whereas for other pairs there was no such bias. In general, feeding was greater on the animal known to have lower rate of host defensive behaviour. Results suggest that relatively slight differences in the inherent defensive behaviour of cattle produce large difference in host-specific feeding rates when the hosts are adjacent. For flies attracted to pair of cattle, < 2% contained blood from both hosts. The DNA profiling technique will be useful in studying the epidemiology of vector-borne diseases of livestock.

Animals↗
PubMed2000

World-wide genetic differentiation of Eubalaena: questioning the number of right whale species.

Few studies have examined systematic relationships of right whales (Eubalaena spp.) since the original species descriptions, even though they are one of the most endangered large whales. Little morphological evidence exists to support the current species designations for Eubalaena glacialis in the northern hemisphere and E. australis in the southern hemisphere. Differences in migratory behaviour or antitropical distribution between right whales in each hemisphere are considered a barrier to gene flow and maintain the current species distinctions and geographical populations. However, these distinctions between populations have remained controversial and no study has included an analysis of all right whales from the three major ocean basins. To address issues of genetic differentiation and relationships among right whales, we have compiled a database of mitochondrial DNA control region sequences from right whales representing populations in all three ocean basins that consist of: western North Atlantic E. glacialis, multiple geographically distributed populations of E. australis and the first molecular analysis of historical and recent samples of E. glacialis from the western and eastern North Pacific Ocean. Diagnostic characters, as well as phylogenetic and phylogeographic analyses, support the possibility that three distinct maternal lineages exist in right whales, with North Pacific E. glacialis being more closely related to E. australis than to North Atlantic E. glacialis. Our genetic results provide unequivocal character support for the two usually recognized species and a third distinct genetic lineage in the North Pacific under the Phylogenetic Species Concept, as well as levels of genetic diversity among right whales world-wide.

Animals↗
PubMed1999

Mitochondrial DNA analysis of sympatric morphotypes of bottlenose dolphins (genus: Tursiops) in Chinese waters.

The classification within the bottlenose dolphin (genus Tursiops) is controversial. Although many morphological variants exist, most authors have concluded that the genus is composed of a single species, Tursiops truncatus (Montagu 1821). Two distinct morphotypes of bottlenose dolphins, which have been referred to as T. truncatus and T. aduncus, exist in sympatry in Chinese waters. Comparisons of a 386-bp fragment of the mitochondrial DNA (mtDNA) control region (n = 47) indicated that the two sympatric morphotypes were genetically distinct, with seven fixed site differences and a sequence divergence of approximately 4.4%. Phylogenetic analyses using maximum likelihood, neighbour-joining and maximum parsimony approaches showed that the truncatus-type dolphins from Chinese waters were more closely related to Atlantic Ocean truncatus-type than to the sympatric aduncus-type dolphins. The Atlantic truncatus-type dolphins also shared the same diagnostic sites that separated Chinese truncatus-type from aduncus-type dolphins. The molecular data agreed completely with the morphological classifications of the specimens. This congruence is strong evidence that the sympatric morphotypes in Chinese waters are reproductively isolated and comprise two distinct species. These findings have important implications for the conservation of bottlenose dolphins in Chinese waters.

Animals↗
PubMed1998

Sequence variation at the major histocompatibility complex DRB loci in beluga (Delphinapterus leucas) and narwhal (Monodon monoceros).

The variation at loci with similarity to DRB class II major histocompatibility complex loci was assessed in 313 beluga collected from 13 sampling locations across North America, and 11 narwhal collected in the Canadian high Arctic. Variation was assessed by amplification of exon 2, which codes for the peptide binding region, via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded conformation polymorphism analysis. Two DRB loci were identified in beluga: DRB1, a polymorphic locus, and, DRB2, a monomorphic locus. Eight alleles representing five distinct lineages (based on sequence similarity) were found at the beluga DRB1 locus. Although the relative number of alleles is low when compared with terrestrial mammals, the amino acid variation found among the lineages is moderate. At the DRB1 locus, the average number of nonsynonymous substitutions per site is greater than the average number of synonymous substitutions per site (0.0806 : 0.0207, respectively; P<0.01). Most of the 31 amino acid substitutions do not conserve the physiochemical properties of the residue, and 21 of these are located at positions implicated as forming pockets responsible for the selective binding of foreign peptide side chains. Only DRB1 variation was examined in 11 narwhal, revealing a low amount of variation. These data are consistent with an important role for the DRB1 locus in the cellular immune response of beluga. In addition, the ratio of nonsynonymous to synonymous substitutions is similar to that among primate alleles, arguing against a reduction in the balancing selection pressure in the marine environment. Two hypotheses may explain the modest amount of Mhc variation when compared with terrestrial mammals: small population sizes at speciation or a reduced neutral substitution rate in cetaceans.

Alleles↗
PubMed1998

Sex identification of elk (Cervus elaphus canadensis), moose (Alces alces), and white-tailed deer (Odocoileus virginianus) using the polymerase chain reaction.

We have developed a PCR-based protocol to determine the gender of tissue samples originating from elk (Cervus elaphus canadensis), moose (Alces alces) and white-tailed deer (Odocoileus virginianus). The technique simultaneously amplifies a conserved region of the sex-determining gene on the Y-chromosome (Sry) and a region of the Fragile X mental retardation gene (Fmr-1). The multiplex nature of this protocol allows the determination of gender using the Sry marker with the Fmr-1 marker providing an internal control. This technique is applicable to the enforcement of the validation tag system for game species. Data are provided from a wildlife investigation in Ontario.

Animals↗
PubMed1996

A rapid, reliable, and inexpensive method for detection of di- and trinucleotide repeat markers and disease loci from dried blood spots.

We used a rapid and inexpensive method for studying the FMR1 CGG-repeat from dried blood spots, prepared from heel pricks, finger pricks, or an aliquot of blood from a venipuncture. The procedure includes a single tube for preparation of template DNA for PCR and minimal handling, avoiding opportunities for mislabelling specimens and loss of template. We extended the protocol to numerous di- and trinucleotide repeat markers and disease loci, including FRAXE, FRAXF, DXS548, DRPLA, and ZFY. The use of a highly reliable and very inexpensive method which employs blood spots as a source for target DNA means that newborn Guthrie cards can be used to establish allele frequencies for linkage disequilibrium studies, that large populations can be screened for genetic disorders, and that mapping studies can proceed rapidly even when only small amounts of blood are available from key family members.

Base Sequence↗
PubMed1996

Lack of expansion of triplet repeats in the FMR1, FRAXE, and FRAXF loci in male multiplex families with autism and pervasive developmental disorders.

Sib, twin, and family studies have shown that a genetic cause exists in many cases of autism, with a portion of cases associated with a fragile X chromosome. Three folate-sensitive fragile sites in the Xq27-->Xq28 region have been cloned and found to have polymorphic trinucleotide repeats at the respective sites; these repeats are amplified and methylated in individuals who are positive for the different fragile sites. We have tested affected boys and their mothers from 19 families with two autistic/PDD boys for amplification and/or instability of the triplet repeats at these loci and concordance of inheritance of alleles by affected brothers. In all cases, the triplet repeat numbers were within the normal range, with no individuals having expanded or premutation-size alleles. For each locus, there was no evidence for an increased frequency of concordance, indicating that mutations within these genes are unlikely to be responsible for the autistic/PDD phenotypes in the affected boys. Thus, we think it is important to retest those autistic individuals who were cytogenetically positive for a fragile X chromosome, particularly cases where there is no family history of the fragile X syndrome, using the more accurate DNA-based testing procedures.

Autistic Disorder↗
PubMed1996

Trinucleotide repeat expansion in the FRAXE locus is not common among institutionalized individuals with non-specific developmental disabilities.

Expansion of a polymorphic GCC-repeat at the FRAXE locus has been associated with expression of chromosome fragility at this site and cognitive impairment in some individuals previously testing negative for CGG-repeat expansion in the fragile X mental retardation-1 (FMR1) gene. To determine the frequency of FRAXE triplet repeat expansion among persons with developmental disability, 396 individuals from two institutions were studied, all of whom were negative for FMR1 repeat expansion. Clinically, there was a wide range of mental impairment, with the majority (61.1%) being severely to profoundly affected. The distribution of FRAXE GCC-repeat numbers in the study population was 5-38: 28 (5.6%) with 10-14 repeats; 366 (73.8%) with 15-19 repeats; 74 (14.9%) with 20-24 repeats; 20 (4.0%) with 25-29 repeats; and 5 (1.0%) with 30-38 repeats, with no individuals demonstrating repeat expansion. One profoundly retarded male was found to have a deletion of about 40 bp. Southern blots of HindIII-digested DNAs from individuals with > or = 26 repeats all showed normal patterns. These results suggest that FRAXE GCC-repeat expansion is not a common cause of developmental disability in institutionalized persons with mild to profound mental retardation.

Adult↗
PubMed1996

Trinucleotide repeats at the FRAXF locus: frequency and distribution in the general population.

FRAXF, the third X-chromosomal fragile site to be cloned, has been shown to harbour a polymorphic compound triplet array: (GCCGTC)n (GCC)n. Expansion and methylation of the GCC-repeat and the neighbouring CpG-rich region result in chromosomal fragility. DNAs from 500 anonymous consecutive newborn males were examined to determine the incidence of various repeat numbers. The range of repeats was from 10-38, with the most common alleles having 14 (52.7%), 12 (16.6%), 21 (9.0%), and 22 (5.2%) triplets. Based on the distribution of repeat numbers, we suggest that the 21-repeat allele resulted from hairpin formation involving 7 GCC-repeats in a 14-repeat allele, accompanied by polymerase slippage. Examination of dinucleotide repeats near the FRAXF repeat will be important in testing this hypothesis. Since the clinical phenotype, if any, of FRAXF is unknown, this database will also be valuable for comparisons with repeat numbers in individuals from special populations.

Chromosome Fragile Sites↗
PubMed1996

Regional localization of an X-linked mental retardation gene to Xp21.1-Xp22.13 (MRX38).

A gene responsible for X-linked mental retardation with macrocephaly and seizures (MRX38) in a family with five affected males in three generations was localized to Xp21.1-p22.13 by linkage analysis. Recombination events placed the gene between DXS1226 distally and DXS1238 proximally, defining an interval of approximately 14 cM. A peak lod score of 2.71 was found with several loci in Xp21.1 (DXS992, DXS1236, DXS997, and DXS1036) at a recombination fraction of zero. The map intervals of 5 X-linked mental retardation loci, MRX2 (Xp22.1-p22.2), MRX19 (Xp22), MRX21 (Xp21.1-p22.3), MRX29 (Xp21.2-p22.1), and MRX32 (Xp21.2-p22.1), and two syndromal mental retardation loci, Partington syndrome (PRTS; Xp22) and Coffin-Lowry syndrome (CLS; Xp22.13-p22.2), overlap this region. As none of these display the same phenotype seen in the family reported here, this X-linked mental retardation locus may represent a new entity.

Adolescent↗
PubMed1995

Absence of lambda immunoglobulin sequences on the supernumerary chromosome of the "cat eye" syndrome.

The supernumerary bisatellited chromosome causing the "cat eye" syndrome (CES) is of chromosome 22 origin and consists of an inverted duplication of the 22pter-->22q11.2 region. To determine the extent of involvement of band q11.2 on the bisatellited chromosome, copy number assessment of sequences homologous to cloned lambda immunoglobulin (lambda Ig) gene region probes was carried out on DNA from individuals with CES using densitometric analysis of Southern blots. None of the 10 lambda Ig sequences studied was found in increased copy number in DNA from any of the 10 CES individuals tested, indicating that these sequences are not present on the supernumerary chromosome. The breakpoints involved in the generation of the bisatellited supernumerary chromosome associated with CES are therefore proximal to the lambda Ig gene region.

Anal Canal↗
PubMed1995

Characterization of a lymphoblastoid line deleted for lambda immunglobulin genes.

While characterizing the cat eye syndrome (CES) supernumerary chromosome for the presence of lambda immunoglobulin gene region sequences, a lymphoblastoid cell line from one CES patient was identified in which there was selection of cells deleted for some IGLC and IGLV genes. Two distinct deletions, one on each chromosome 22, were identified, presumably arising from independent somatic recombination events occurring during B-lymphocyte differentiation. The extent of the deleted regions was determined using probes from the various IGLV subgroups and they each cover at least 82 kilobases. The precise definition of the deletions was not possible because of conservation of some restriction sites in the IGLV region. The cell line was used to map putative IGLV genes within the recombinant phage lambda V lambda 135 to the distal part of the IGLV gene region. Since the deletions are relatively small, the cell line will be valuable for mapping IGLV genes in the distal part of this region.

Cell Line↗
PubMed1995

Sequence variation at the major histocompatibility complex locus DQ beta in beluga whales (Delphinapterus leucas)

Genetic variation at the Major Histocompatibility Complex locus DQ beta was analyzed in 233 beluga whales (Delphinapterus leucas) from seven populations: St. Lawrence Estuary, eastern Beaufort Sea, eastern Chukchi Sea, western Hudson Bay, eastern Hudson Bay, southeastern Baffin Island, and High Arctic and in 12 narwhals (Monodon monoceros) sympatric with the High Arctic beluga population. Variation was assessed by amplification of the exon coding for the peptide binding region via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded conformation polymorphism analysis. Five alleles were found across the beluga populations and one in the narwhal. Pairwise comparisons of these alleles showed a 5:1 ratio of nonsynonymous to synonymous substitutions per site leading to eight amino acid differences, five of which were nonconservative substitutions, centered around positions previously shown to be important for peptide binding. Although the amount of allelic variation is low when compared with terrestrial mammals, the nature of the substitutions in the peptide binding sites indicates an important role for the DQ beta locus in the cellular immune response of beluga whales. Comparisons of allele frequencies among populations show the High Arctic population to be different (P < or = .005) from the other beluga populations surveyed. In these other populations an allele, Dele-DQ beta*0101-2, was found in 98% of the animals, while in the High Arctic it was found in only 52% of the animals. Two other alleles were found at high frequencies in the High Arctic population, one being very similar to the single allele found in narwhal.

Alleles↗