Microsatellite based genetic diversity and mitochondrial DNA D-Loop variation in economically important goat breeds of Pakistan

The present study was undertaken to analyze the genetic diversity of five economically important goat breeds of Pakistan, Beetal, Kaghani, Teddy, Nachi and Pahari. Fifteen microsatellite loci recommended by ISAG/FAO guidelines were investigated for measures of genetic variability, differentiation and population structure. The genetic variability in terms of allelic diversity and heterozygosity were moderate. The estimated inbreeding coefficient was low in all the investigated goat breeds and not significant. Overall, the populations were less diverse than Eurasian goat breeds, but did not exhibit signs of loss of diversity. Analysis of molecular variance (AMOVA) showed breed differences accounted for 5.42% of total genetic variation indicating low to moderate genetic differentiation among the investigated goat breeds. The genetic structure analysis revealed Teddy, Pahari, and Nachi as distinct breeds, while Beetal and Kaghani form a single genetic group distinct from the other three goats. The mitochondrial DNA control region sequences showed a total of 60 distinct haplotypes belonging to two major maternal lineages A and B1 with a frequency of 76.9% and 23.1% respectively. Comparison of mtDNA sequences from Pakistani, Indian and Iranian goats indicated distinct evolutionary history for Teddy, Beetal, Nachi and Pahari goats different from that of Indian and Iranian goats

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response

Objective The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Methods Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. Results In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Conclusion Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures