Mitochondrial genomes from modern horses reveal the major haplogroups that underwent domestication

Archaeological and genetic evidence concerning the time and mode of wild horse (Equus ferus) domestication is still debated. High levels of genetic diversity in horse mtDNA have been detected when analyzing the control region; recurrent mutations, however, tend to blur the structure of the phylogenetic tree. Here, we brought the horse mtDNA phylogeny to the highest level of molecular resolution by analyzing 83 mitochondrial genomes from modern horses across Asia, Europe, the Middle East, and the Americas. Our data reveal 18 major haplogroups (A-R) with radiation times that are mostly confined to the Neolithic and later periods and place the root of the phylogeny corresponding to the Ancestral Mare Mitogenome at ~130-160 thousand years ago. All haplogroups were detected in modern horses from Asia, but F was only found in E. przewalskii--the only remaining wild horse. Therefore, a wide range of matrilineal lineages from the extinct E. ferus underwent domestication in the Eurasian steppes during the Eneolithic period and were transmitted to modern E. caballus breeds. Importantly, now that the major horse haplogroups have been defined, each with diagnostic mutational motifs (in both the coding and control regions), these haplotypes could be easily used to (i) classify well-preserved ancient remains, (ii) (re)assess the haplogroup variation of modern breeds, including Thoroughbreds, and (iii) evaluate the possible role of mtDNA backgrounds in racehorse performance.     

Immunoglobulin and complement depositions in the liver of chronic hepatitis patients

BACKGROUND/AIMS: Liver biopsy is a cornerstone in the management of chronic hepatitis patients. In biopsy, liver cell damage as well as severity of inflammatory cell infiltration in the parenchyma and portal tracts are evaluated. There are some other inflammatory markers such as complements (C) and immunoglobulins (Ig), which are involved in the pathogenesis of inflammation. This study was carried out to investigate the status of Ig and C depositions in the liver of chronic hepatitis cases. METHODOLOGY: Two biopsy samples were taken from patients who were scheduled for liver biopsy for chronic hepatitis. The acetone fixed sections were incubated with fluorescin-conjugated anti human IgG, IgA, IgM, C3 and C4. Ten samples of non-hepatitis control cases were provided during elective cholecystectomy. RESULTS: Deposition of IgG, IgM, and Cs were seen in the parenchyma in HBV, HCV and non viral hepatitis cases. The parenchyma of control liver did not show any deposition of IgG, IgM, and Cs. IgA was found in the parenchyma of 3 control cases. C3 deposition in the parenchyma had significant association with enzyme rising in HCV (p=0.001) and non viral groups (p=0.004). C4 deposition in the parenchyma was also associated with enzyme rising in HCV cases (p=0.01). There was an association between ALT elevations with the presence of IgM in the parenchyma in HBV (p=0.01) and HCV (p=0.03) groups. Mantel-Haenszel chi2 test (for evaluation of the effects of stage and grade) confirmed that the depositions of C3 and C4 in HCV and C3 in nonviral hepatitis have positive association with enzyme rising. CONCLUSIONS: Presence of IgM, IgG, C3, and C4 in the liver parenchyma is abnormal and may be helpful in histological evaluation in chronic hepatitis. Parenchymal (but not portal) depositions of C3 and C4 in HCV and non-viral hepatitis cases show close association with elevation of liver enzymes.     

Use of D11S2179 and D11S1343 as markers for prenatal diagnosis of ataxia telangiectasia in Iranian patients

Ataxia telangiectasia (AT) is an autosomal recessive disorder with an estimated prevalence of 1/40,000 to 1/100,000 in reported populations. There is a 25% possibility for having an affected child when parents are carriers for the ATM gene mutation. There is no cure available for this disease and prenatal testing is strongly recommended for prevention of this disease. Although the preferred method is the direct mutation analysis of the ATM gene, the large size of the ATM gene with 63 exons and the large number of possible mutations in patients considerably limit efficiency of mutation analysis as a diagnostic choice. Indirect method is a better tool when parents are not carriers of founder mutation and pass different mutations to their children. Indirect molecular diagnosis using ATM-related molecular markers facilitates prenatal diagnosis of AT children. In this study, four molecular markers: D11S2179, D11S1787, D11S535, D11S1343 are genotyped in 19 unrelated families from different regions of Iran. Those markers are amplified using extracted sequence primers from the Gene Bank with their described PCR conditions. Amplified products were separated using denaturing PAGE gels, and data were analyzed to detect their pattern of inheritance in each family. In all families, segregation of alleles was according to Mendelian inheritance, and affected chromosomes were distinguishable from unaffected ones. All carriers and affected patients were diagnosed accurately. Thus, this method is effectively useful in prenatal diagnosis of AT.     

Boosting effect of bisphosphonates on osteoconductive materials: a histologic in vivo evaluation

BACKGROUND AND OBJECTIVE: The effect on bone regeneration, of adding pamidronate disodium to bovine-derived hydroxyapatite, was histologically evaluated, using the sheep bone model. MATERIAL AND METHODS: Twenty-four intrabony defects were prepared in the lower jaw of eight sheep using trephine 6 mm burs. One cavity was left unfilled and the other two were filled with bovine-derived hydroxyapatite (BioOss) alone (control group) or with bovine-derived hydroxyapatite mixed with pamidronate disodium (Aredia) (case group), respectively. After 6 wk, the animals were killed and the coded samples observed using an optical microscope. The percentage of regenerated bone, number of osteoclasts and amount of inflammation was recorded. Statistical analysis was carried out using chi-square and Mann-Whitney U-tests. RESULTS: The results manifested a significant difference in the amount of bone formation, with the most being observed in the case group and the least in the negative-control group (p<0.001). Significantly fewer osteoclasts were observed in the case group than in the other groups (p<0.001). The amount of inflammation did not seem to differ within the case and control groups (p>0.05). CONCLUSION: Adding pamidronate disodium to bovine-derived hydroxyapatite improves its osteoconductive and regenerative specifications. Further study should determine the systemic effects of a single local administration of these drugs, and their appropriate dose and type, with minimal risk.     

A novel mutation in the transactivation-regulating domain of the androgen receptor in a patient with azoospermia

Genetic factors including Y chromosome microdeletions and androgen receptor (AR) gene mutations are responsible for male infertility. In the present study, genetic analysis was performed in an infertile Iranian male with azoospermia. Multiplex polymerase chain reaction with 6 sequence-tagged site markers on the Yq11 chromosome revealed no microdeletions in the Y chromosome. Single-strand conformational polymorphism and sequencing analyses detected a 1510C→A transversion in exon 1 of the AR gene, which resulted in a p.Pro504Thr substitution in the transactivation domain of the protein. The present study suggested that mutations in the AR gene might be responsible for some cases of idiopathic infertility, and therefore, molecular analyses may be useful for genetic counseling of candidates with regard to the use of assisted reproductive techniques.     

Alexander Disease: Report of Two Unrelated Infantile Form Cases,Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran

Background

Alexander disease (AD) is a sporadic leukodystrophy that predominantly affects infants and children and usually results in death within ten years after onset. The infantile form comprises the most of affected individuals. It presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly and frontal bossing, seizures, pyramidal signs and ataxia. The diagnosis is based on magnetic resonance imaging (MRI) findings and confirmed by GFAP gene molecular testing. GFAP gene encodes glial fibrillary acidic protein, is the only gene in which mutation is currently known to cause AD which is inherited in autosomal dominant manner.

Case Presentation

In this article we report the first two Iranian cases of infantile AD and their clinical, brain MRI and molecular findings. We report two novel mutations too in the GFAP gene that are associated with infantile form of AD.

Conclusion

GFAP gene mutations are a reliable marker for infantile AD diagnosed according to clinical and MRI defined criteria. A genotype-phenotype correlation had been discerned for the two most frequently reported GFAP gene mutations in infantile type of AD (R79 and R239), with the phenotype of the R79 mutations appearing much less severe than that of the R239 mutations. Our findings confirm this theory.     

ERCC1 intron 1 was associated with breast cancer risk

Introduction

There are numerous studies addressing associations of polymorphisms in DNA repair genes and cancer risks because accurate and efficient DNA repair is crucial to genomic integrity and fidelity. ERCC1 is important in DNA nucleotide excision repair.

Material and methods

We genotyped constitutive variants of ERCC1 in approximately 300 adults with breast adenocarcinoma and 126 controls of Iranian women. In total, 426 Iranian sporadic breast cancer affected women compared to the control group were studied by PCR-RFLP for ERCC1 variant.

Results

The genotype ERCC1 TT has the highest frequency in both groups (36.6 in patients and 8.5 in controls). The genotype ERCC1 was the most important risk factor in our population [GG/AA odds ratio: 0.692, 95% confidence interval (CI): 0.4-1.199, p = 0.188; GG/AG odds ratio: 3.333, 95% CI: 1.917-5.795, p = 0.001; AA/AG odds ratio: 0.208, 95% CI: 0.124-0.348, p = 0.342].

Conclusions

Our patients was associated with breast cancer risk.     

Evaluation of deltamethrin-impregnated bed nets and curtains for control of zoonotic cutaneous leishmaniasis in a hyperendemic area of Iran

In the study carried out in the rural district of Borkhar (Isfahan, Iran) from March 2003 to March 2004 efficacy of deltamethrin impregnated bed nets (IBs) and curtains (ICs), polyester mesh size 156 holes/ inch2, (25 holes/cm2) were compared to that of non-impregnated bed nets (NIBs) and curtains (NICs), in relation to zoonotic cutaneous leishmaniasis (ZCL) control. Deltamethrin impregnated bed nets and curtains at 25 mg a.i./m2 were distributed among 168 households in one of the villages and NIBs plus NICs among the same number of households in another village. In the third village similar numbers of households were used as control. Health education messages were disseminated to ensure the population's compliance with the proper use of bed nets and curtains in the two intervention areas. Entomological surveys using sticky paper traps were carried out in ten households in each village for the collection of sand flies from indoors and outdoors, every two weeks to assess the impact of insecticide impregnated bed nets and curtains on the density of Phlebotomus papatasi. Deltamethrin susceptibility tests and also bioassay tests were carried out on this species by WHO standard method. Case findings were done by house-to-house visits once a season and all the inhabitants of the selected households in each village were examined. The results showed that IBs and ICs can provide a definite personal protection against sand fly bites and interrupted the transmission of ZCL in the intervention village. NIBs and NICs did not provide any protection against the disease. There was no significant difference in monthly density of P. papatasi in indoors and outdoors among the villages (P > 0.05). Susceptibility tests showed that this species was susceptible to deltamethrin in the field population in the area. Bioassays confirmed that the treated nets with deltamethrin remain effective for more than three months and was an excellent mean of individual protection. It is recommended that IBs and ICs can be used widely in the control of ZCL in other similar foci such as hyperendemic and mesoendemic areas of Iran.     

Association Between Glycemia, Serum Lipoproteins, and the Risk of Oral Leukoplakia: The population-based Study of Health in Pomerania (SHIP)

OBJECTIVE

Oral leukoplakia is an oral lesion with a premalignant character. Besides smoking and alcohol, diabetes could be a risk factor. The aim is to search for such an association.

RESEARCH DESIGN AND METHODS

Subjects with leukoplakia (N = 123) from the population-based Study of Health in Pomerania (SHIP) were matched 1:2 for age and sex with unaffected control subjects. Behavioral and lifestyle factors were assessed by a questionnaire. Lipoprotein concentrations, glycemia, and inflammation parameters were determined.

RESULTS

Subjects with oral leukoplakia showed higher levels of diabetes-related metabolites, a higher LDL/HDL cholesterol ratio (P = 0.004), and higher A1C (P = 0.002), and they were more frequently smokers (P < 0.001). Assessed by conditional logistic regression, the probability of leukoplakia increases with current smoking (odds ratio 2.20 [95% CI 1.16–4.17]) and higher levels of A1C (1.51 [95% CI 1.08–2.12]), revealing interaction between both factors (P = 0.012).

CONCLUSIONS

Diabetes is associated with the risk of oral leukoplakia, which is exaggerated by smoking. The risk is positively correlated with A1C concentrations.Diabetes is related to different pathological states in the oral cavity including premalignant and malignant lesions (1–3). Leukoplakia is an asymptomatic, potentially malignant lesion in the oral mucosa. Between <1 and 18% of oral premalignant lesions will develop into oral cancer (4). Smoking and drinking alcohol are main risk factors for this disease (5). Even though there is a strong association between diabetes and leukoplakia, a causal mechanism for that has not been elucidated. In the present study, we assess the effect of metabolic risk factors on oral leukoplakia.