The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency

Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs -/- mice. However, these observations are based on independent studies with varying genetic backgrounds. Here, we generated ku80-/-, dna-pkcs -/- and double knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their lifespan, end of life pathology and mutation frequency in liver a

Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis.

Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1-10% in the general population, notifications of symptomatic pertussis only comprise 0.01-0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection

The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency

Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs -/- mice. However, these observations are based on independent studies with varying genetic backgrounds. Here, we generated ku80-/-, dna-pkcs -/- and double knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their lifespan, end of life pathology and mutation frequency in liver a

Characteristics of symptomatic pertussis patients.

<p>Characteristics of symptomatic pertussis patients.</p

Genotype frequencies and OR for the <i>VDR</i>, <i>TNFα</i>, <i>IL17</i>, <i>MBL2</i> and <i>IL10</i> SNPs in the pertussis patient group and control group.

<p>Genotype frequencies and OR for the <i>VDR</i>, <i>TNFα</i>, <i>IL17</i>, <i>MBL2</i> and <i>IL10</i> SNPs in the pertussis patient group and control group.</p

Allele frequencies and OR for the <i>VDR</i>, <i>TNFα</i>, <i>IL17</i>, <i>MBL2</i> and <i>IL10</i> SNPs in the pertussis patient group and control group.

<p>Allele frequencies and OR for the <i>VDR</i>, <i>TNFα</i>, <i>IL17</i>, <i>MBL2</i> and <i>IL10</i> SNPs in the pertussis patient group and control group.</p

Association <i>VDR</i> SNP with pertussis in patients with symptoms that persisted for longer than 4 weeks.

<p>Association <i>VDR</i> SNP with pertussis in patients with symptoms that persisted for longer than 4 weeks.</p

Distribution of <i>VDR</i> genotypes and alleles in the pertussis patient group according to the reported duration of symptoms.

<p>Distribution of <i>VDR</i> genotypes and alleles in the pertussis patient group according to the reported duration of symptoms.</p