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J R Shaffer,
X Wang,
E Feingold,
M Lee,
F Begum,
D E Weeks,
K T Cuenco,
M M Barmada,
S K Wendell,
D R Crosslin, [......],
J C Murray,
R J Weyant,
R Crout,
D W McNeil,
S M Levy, R L Slayton,
M C Willing,
B Broffitt,
A R Vieira,
M L Marazita
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ABSTRACT: Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries.
Journal of dental research 09/2011; 90(12):1457-62. · 3.46 Impact Factor
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ABSTRACT: Polymorphic, acidic proline-rich proteins (PRPs) in saliva influence the attachment of bacteria associated with caries. Our aims were to detect one of three acidic PRP alleles of the PRH1 locus (Db) using polymerase chain-reaction (PCR) on genomic DNA, and to determine its association with caries. DNA was obtained from buccal swabs from Caucasian and African-American children, and their caries experience was recorded. PCR primers designed around exon 3 of the PRH1 locus gave a 416-base product representing Db and a 353-base product representing the other two alleles (Pa or Pif). In Caucasians, Db gene frequency was 14%, similar to Db protein from parotid saliva. In African-Americans, however, it was 37%, 18% lower than Db from parotid saliva (reported previously). Compared with African-Americans, all Caucasians had significantly greater Streptococcus mutans colonization, but only Db-negative Caucasians had significantly more caries. Alleles linked to Db may explain racial differences in caries experience.
Journal of Dental Research 01/2008; 86(12):1176-80. · 3.49 Impact Factor
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ABSTRACT: The purpose of this study was to identify genetic factors that contribute to dental caries susceptibility, either alone or in combination with environmental factors. Dental examinations were performed and buccal swab samples collected from 3- to 5-year-old children with at least 4 surfaces of decay, or with no evidence of decay. SNP assays for each of 6 candidate genes were performed for all cases and controls. Chi-square analysis and regression analysis were used for the evaluation of individual gene effects, environmental effects, and gene-environment interactions. There were no significant associations between single candidate genes and caries susceptibility. Levels of S. mutans were positively and Lactobacilli were negatively associated with caries. Regression analysis revealed a significant interaction between tuftelin and S. mutans, with 26.8% of the variation in dmfs explained by the interaction. Future research will focus on the identification of these additional factors and the development of functional assays so that these interactions can be better understood.
Journal of Dental Research 09/2005; 84(8):711-4. · 3.49 Impact Factor
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ABSTRACT: Osteogenesis imperfecta (OI) is a heterogeneous disorder of type I collagen resulting in varying degrees of severity. The mildest form of OI (Type I) is associated with bone fragility, normal or near normal stature and blue sclerae. All forms of OI are the result of mutations in COL1A1 or COL1A2, the genes that encode the proalpha1(I) and proalpha2(I) chains of type I collagen, respectively. Mutations identified in patients with OI type I lead to premature termination codons and allele-specific reductions of nuclear mRNA (termed nonsense-mediated mRNA decay or NMD), resulting in a COL1A1 null allele. In mammals, this process primarily effects RNA that co-purifies with the nuclear fraction of the cell. Using a semi-quantitative RT-PCR assay, we compare the relative amounts of normal and mutant transcripts in unprocessed hnRNA and mature mRNA isolated from the nuclear fraction of cells from 11 OI type I individuals with previously identified mutations distributed throughout the COL1A1 gene. While we detect about equal amounts of normal and mutant hnRNA from each cell strain, there is preferential reduction in the relative amount of mutant mRNA when compared to normal; only the cell strain with a mutation in the last exon escapes the major effects of NMD. Our data indicate that NMD targets mRNA rather than hnRNA for degradation, and that this occurs either during or after splicing but prior to cytoplasmic translation.
Matrix Biology 03/2000; 19(1):1-9. · 3.30 Impact Factor
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ABSTRACT: Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type 1. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type 1.
The American Journal of Human Genetics 11/1996; 59(4):799-809. · 10.60 Impact Factor
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ABSTRACT: Osteogenesis imperfecta type I results from decreased production of structurally normal type I collagen as a result of a COL1A1 "null" allele. Steady state amounts of COL1A1 mRNA are reduced in both the nucleus and cytoplasm of dermal fibroblasts from most affected subjects. Mutations involving key regulatory sequences in the COL1A1 promoter, such as the TATAAA and CCAAAT boxes, could alter steady state levels of mRNA, and therefore lead to this phenotype. To determine the frequency of such mutations in OI type I cell strains, we used PCR amplified genomic DNA in conjunction with denaturing gradient gel electrophoresis (DGGE) and SSCP, to screen the 5' untranslated domain, exon 1, and a small portion of intron 1 of the COL1A1 gene. In addition, direct sequence analysis was performed on an amplified genomic DNA fragment that included the TATAAA and CCAAAT boxes. Forty unrelated probands with OI type I, in whom no causative mutation was known, were included in the study. No mutations were included in the study. No mutations were identified in either the TATAAA or CCAAAT boxes in any of the affected people. In addition, there was little evidence of sequence diversity among any of the 40 subjects. These data suggest that mutations in the COL1A1 promoter do not play a significant role in the aetiology of OI type I.
Journal of Medical Genetics 10/1995; 32(9):697-700. · 6.36 Impact Factor
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ABSTRACT: Osteogenesis imperfecta (OI) type I is the mildest form of inherited brittle-bone disease. Dermal fibroblasts from most affected individuals produce about half the usual amount of type I procollagen, as a result of a COL1A1 "null" allele. Using PCR amplification of genomic DNA from affected individuals, followed by denaturing gradient gel electrophoresis (DGGE) and SSCP, we identified seven different COL1A1 gene mutations in eight unrelated families with OI type I. Three families have single nucleotide substitutions that alter 5' donor splice sites; two of these unrelated families have the same mutation. One family has a point mutation, in an exon, that creates a premature termination codon, and four have small deletions or insertions, within exons, that create translational frameshifts and new termination codons downstream of the mutation sites. Each mutation leads to both marked reduction in steady-state levels of mRNA from the mutant allele and a quantitative decrease in type I procollagen production. Our data demonstrate that different molecular mechanisms that have the same effect on type I collagen production result in the same clinical phenotype.
The American Journal of Human Genetics 11/1994; 55(4):638-47. · 10.60 Impact Factor
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ABSTRACT: Enamel hypoplasia is of interest to both the clinician and the basic scientist because it may indicate an increased risk for caries and can contribute to the understanding of enamel development. The purpose of this paper is to report the prevalence of enamel hypoplasia and isolated enamel opacities in a cohort of healthy, well-nourished children in Iowa.
The study sample consisted of 698 children examined at 4-5 years of age. Individual tooth surfaces were scored for the presence of enamel hypoplasia (EH) and isolated enamel opacities. Prevalence of EH and isolated opacities were determined by tooth type and by gender.
Six percent of the children examined had at least one tooth with EH; 27% had at least one tooth with isolated enamel opacities. There was no difference in the prevalence of EH between boys and girls, but significantly more boys than girls had enamel opacities.
The prevalence of enamel defects in this study group is comparable to that seen in other studies of normally developed children except that in this study, the primary tooth types most commonly affected with enamel hypoplasia or isolated opacities were mandibular second molars and maxillary second molars, respectively.
Pediatric dentistry 23(1):32-6. · 1.02 Impact Factor
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ABSTRACT: The purpose of this study was to determine parental perception of the oral health needs of children with disabilities and whether or not they had difficulty obtaining dental care. A survey of parents of children enrolled in the Medicaid Supplemental Security Income (SSI) health plan in Iowa showed that 68 percent of children had dental needs during the previous year. Of these children, parents reported that 9.4 percent had a 'big problem' getting that care, 8.1 percent had a 'small problem' getting care and 82.5 percent stated that getting dental care was 'not a problem.' There were significantly more dental needs reported in children in the older age groups (> or = 5 years) and those with more years of experience in the program (p < 0.01). Further study is necessary to determine the types of barriers faced by those in the SSI program seeking dental care.
ASDC journal of dentistry for children. 68(3):206-10, 152.
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R L Slayton
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ABSTRACT: The term Riga-Fede disease has been used historically to describe a traumatic ulceration that occurs on the ventral surface of the tongue in neonates and infants. It is frequently associated with natal or neonatal teeth but may also occur in older infants after the eruption of primary lower incisors. Failure to diagnose and properly treat this lesion can result in dehydration and inadequate nutrient intake for the infant. Treatment should begin conservatively and should focus on eliminating the source of trauma. A case is presented in which modification of sharp tooth surfaces by the Pediatric Dentist and changes in feeding techniques by the parent were used successfully to resolve this lesion. By working together, the parent and the Pediatric Dentist can achieve positive results in a short period of time with minimal trauma to the infant.
Pediatric dentistry 22(5):413-4. · 1.02 Impact Factor
