A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination.

Novel mutations in myelin and myelin-associated genes have provided important information on oligodendrocytes and myelin and the effects of their disruption on the normal developmental process of myelination of the central nervous system (CNS). We report here a mutation in the folliculin-interacting protein 2 (FNIP2) gene in the Weimaraner dog that results in hypomyelination of the brain and a tract-specific myelin defect in the spinal cord. This myelination disruption results in a notable tremor syndrome from which affected dogs recover with time.

Deficiency of FRAS1-related extracellular matrix 1 (FREM1) causes congenital diaphragmatic hernia in humans and mice.

Congenital diaphragmatic hernia (CDH) is a common life-threatening birth defect. Recessive mutations in the FRAS1-related extracellular matrix 1 (FREM1) gene have been shown to cause bifid nose with or without anorectal and renal anomalies (BNAR) syndrome and Manitoba oculotrichoanal (MOTA) syndrome, but have not been previously implicated in the development of CDH. We have identified a female child with an isolated left-sided posterolateral CDH covered by a membranous sac who had no features suggestive of BNAR or MOTA syndromes.

The chicken frizzle feather is due to an α-keratin (KRT75) mutation that causes a defective rachis.

Feathers have complex forms and are an excellent model to study the development and evolution of morphologies. Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation. This study focused on the gene F, underlying the frizzle feather trait that has a characteristic curled feather rachis and barbs in domestic chickens.

Impact of restricted marital practices on genetic variation in an endogamous Gujarati group.

Recent studies have examined the influence on patterns of human genetic variation of a variety of cultural practices. In India, centuries-old marriage customs have introduced extensive social structuring into the contemporary population, potentially with significant consequences for genetic variation. Social stratification in India is evident as social classes that are defined by endogamous groups known as castes.

X-linked congenital hypertrichosis syndrome is associated with interchromosomal insertions mediated by a human-specific palindrome near SOX3.

X-linked congenital generalized hypertrichosis (CGH), an extremely rare condition characterized by universal overgrowth of terminal hair, was first mapped to chromosome Xq24-q27.1 in a Mexican family. However, the underlying genetic defect remains unknown.

Prevalence of common disease-associated variants in Asian Indians.

Background: Asian Indians display a high prevalence of diseases linked to changes in diet and environment that have arisen as their lifestyle has become more westernized. Using 1200 genome-wide polymorphisms in 432 individuals from 15 Indian language groups, we have recently shown that: (i) Indians constitute a distinct population-genetic cluster, and (ii) despite the geographic and linguistic diversity of the groups they exhibit a relatively low level of genetic heterogeneity.

Results: We investigated the prevalence of common polymorphisms that have been associated with diseases, such as atherosclerosis (ALOX5), hypertension (CYP3A5, AGT, GNB3), diabetes (CAPN10, TCF7L2, PTPN22), prostate cancer (DG8S737, rs1447295), Hirschsprung disease (RET), and age-related macular degeneration (CFH, LOC387715).

Inherited dental anomalies: a review and prospects for the future role of clinicians.

Inherited dental anomalies such as hypodontia, supernumerary teeth, enamel defects, and diastema are evident in large segments of most populations. Although treatment options for many of these conditions are ever improving, much remains to be understood about their etiology and pathophysiology. In this review, the authors hope to enthuse dental professionals into aiding the human geneticist by collaborating in studies seeking the underlying genetic cause of dental anomalies and referring patients presenting these conditions to the human geneticist.

Identification of novel genes expressed during mouse tooth development by microarray gene expression analysis.

To identify genes heretofore undiscovered as critical players in the biogenesis of teeth, we have used microarray gene expression analysis of the developing mouse molar tooth (DMT) between postnatal day (P) 1 and P10 to identify genes differentially expressed when compared with 16 control tissues. Of the top 100 genes exhibiting increased expression in the DMT, 29 were found to have been previously associated with tooth development. Differential expression of the remaining 71 genes not previously associated with tooth development was confirmed by quantitative reverse transcription-polymerase chain reaction analysis.

A simple method for DNA isolation from clotted blood extricated rapidly from serum separator tubes.

Background: After clinical laboratory tests have been performed, it can be difficult to obtain DNA without further patient involvement. Although the blood clot remaining within the serum-separation tube after serum collection is a source of DNA, recovery of the clot from the tube is a significant challenge.

Method: We devised a method to efficiently remove clotted blood from the serum-separation gel and extract DNA from clotted whole blood samples, obtaining maximum yield of the DNA without DNA contamination by the separation gel.

Low levels of genetic divergence across geographically and linguistically diverse populations from India.

Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation.

A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3.

Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.

Gene discovery for dental anomalies: a primer for the dental professional.

Background: Thousands of inherited human disorders have been catalogued to date, but the underlying genetic causes of less than 20 percent of those disorders have been discovered.

Type Of Studies Reviewed: The completion of the Human Genome Project (HGP) has made available the DNA sequence of all 24 human chromosomes, thereby allowing the localization of all human genes and, ultimately, determination of their function. Disease gene discovery is being expedited greatly by the data from the HGP, thereby paving the way for determination of the genetic etiology of most of these disorders.

Nonconventional genetic risk factors for cardiovascular disease.

Despite numerous advances made in identifying the genes for rare mendelian forms of cardiovascular disease (CVD), relatively little is known about the common, complex forms at the genetic level. Moreover, most genes that have been associated with CVD, whether they are single gene forms or more common forms of the disease, have primarily been involved in biochemical pathways related to what are considered "conventional" risk factors. However, recent genetic studies have begun to identify genes and pathways associated with CVD that would not be considered to underlie conventional risk factors.

Genes underlying familial hypodontia: a review and discussion of the role of dental hygienists in future research.

Congenitally missing teeth, or hypodontia, is one of the most common abnormalities of the human dentition and has a critical and often lifelong impact on the oral health of affected individuals. Here we review hypodontia and describe the patterns of inheritance it can display. A short review of tooth development and a primer in human genetics are presented.

Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine.

We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry.

Reciprocal crossovers and a positional preference for strand exchange in recombination events resulting in deletion or duplication of chromosome 17p11.2.

Smith-Magenis syndrome (SMS) is caused by an approximately 4-Mb heterozygous interstitial deletion on chromosome 17p11.2 in approximately 80%-90% of affected patients. Three large ( approximately 200 kb), complex, and highly homologous ( approximately 98%) low-copy repeats (LCRs) are located inside or flanking the SMS common deletion.

Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia.

We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9.

Comparative analysis of Schwann cell lines as model systems for myelin gene transcription studies.

Primary and immortalized cultured Schwann cells are commonly utilized in analyses of myelin gene promoters, but few lines are well-characterized in terms of their endogenous expression of myelin genes. This is particularly significant in that cultured Schwann cells typically do not express myelin genes at levels comparable to those observed in vivo. In this study, the steady-state levels of mRNA and protein for five Schwann cell markers (PMP22, P0, MBP, MAG, and LNGF-R) were assessed in primary Schwann cells and six representative Schwann cell lines (RT4-D6P2T, JS-1, RSC96, R3, S16, and S16Y).

Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia.

We recently identified a frame-shift mutation in the PAX9 gene as the underlying cause for hypodontia involving permanent molar teeth segregating in an autosomal dominant pattern in a single large family (Stockton et al. 2000). Here we report a small nuclear family in which a father and his daughter are affected with severe hypodontia, involving agenesis of all primary and permanent molars, evidently caused by deletion of the entire PAX9 gene.