Identification of a shared, common haplotype cosegregating with an SGCB c.544A>C mutation in Indian patients affected with sarcoglycanopathy

Background Sarcoglycanopathies (SG) is the most frequent form of autosomal recessive limb-girdle muscular dystrophies (LGMD) leading to progressive muscle wasting and weakness, predominantly characterized by limb-girdle weakness. LGMDR4 is caused by mutations in SGCB encoding for the beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype cosegregating in 14 SG cases from 13 unrelated families with the likely pathogenic homozygous mutation c.544A>C (p.Thr182Pro) in SGCB. Methods The genotypes of five selected markers (rs10009426, rs6824707, rs2271046, rs35414474 and rs17611952) surrounding the c.544A>C (p.Thr182Pro) were extracted from the variant call format (VCF) generated from whole-exome sequencing (WES) of 14 cases and 14 related family members as controls. The linkage data file was constructed and linkage disequilibrium (LD) plots were generated using HaploView to visualize patterns of LD. Further, haplotype reconstructions based on the 6 markers were conducted using PLINK1.9. using the expectation-maximization (EM) algorithm, an iterative method to find maximum likelihood. Subsequently, the R programming language was used to determine and compare plots of the haplotype frequencies and percentages for both groups to infer the risk haplotypes. Results Four strong LD blocks were identified in control group: rs10009426 to rs6824707 (0.27 kb), rs6824707 to rs2271046 (41.6 kb), rs10009426 to rs2271046 (41.8 kb) and rs35414474 to rs17611952 (0.17 kb) which were absent in the case group. Similarly, a total of nine haplotypes were estimated in cases and controls of which haplotype H1= G, A, T, G, G, T showed significant statistical difference in the frequency between cases and controls. H1 is also observed to cosegregate with c.544A>C (p.Thr182Pro) in the pedigrees of all the cases. Conclusion The identification of c.544A>C (p.Thr182Pro) mutation in 14 cases from India indicates a probable event of founder effect. Further, the H1 haplotype, cosegregating with this mutation, convincingly sheds light on the recent developments in population genetics allowing insights into demographic and population history. This haplotype can also be used as a genetic marker to screen individuals with genetic susceptibility as carriers and provide genetically informed risk stratification and management in the prevention of SG.

Influence of temperature and moisture duration on pathogenic life-history traits of predominant haplotypes of Fusarium circinatum on Pinus spp. in Spain

Pathogen life-history traits influence epidemic development and pathogen adaptive ability to interact with their hosts in different environments. Reduced traits variation may compromise pathogen evolutionary potential which is particularly important for introduced pathogens. Fusarium circinatum (cause of Pine Pitch Canker) is an invasive fungal pathogen in Europe, with current distribution restricted to forest stands of Pinus radiata and P. pinaster in northern Spain and Portugal. This study aimed to quantify pathogenic traits of Spanish isolates of F. circinatum, with two of the strains representing the two dominant haplotypes in the Spanish population. Disease severity was measured on P. radiata, analyzing the influence of temperature and moisture duration on infection as well as the influence of temperature on spore germination, sporulation and mycelial growth. Results indicated that the isolate representing the most common haplotype caused more severe disease on Pinus radiata at 25 and 30ºC compared to the second most common haplotype, but less severe disease at 15ºC. Spore germination was higher for the most common haplotype, which produced more spores at 20 and 25ºC. The isolate showed hyphal melanization at 5ºC, which has been associated with survival and may be important since no resting structures have been described for F. circinatum. Our study determined that longer moisture periods during infection result in more severe disease from 7 to 24 h, regardless of the isolate virulence. This is the first study on virulence of the most abundant haplotypes of F. circinatum in Spain as affected by temperatures and moisture.

Founding mutations explains hot spots of polycystic kidney disease in Southern Spain

Our group identified two pathogenic variants on the PKD1 gene, c.10527_10528delGA and c.7292T>A from unrelated families. They came from two small counties in Granada, with 61 and 26 ADPKD individuals affected. To determine a common ancestor, healthy and ADPKD individuals from these families were genotyped by analyzing four microsatellites located on chromosome 16. Our study identified a common haplotype in all ADPKD individuals. These findings underpin our hypothesis of the founder effect and explains why there is a high frequency of ADPKD in small regions. Determining hot spots of ADPKD will help to better plan health care in the future.

Genetic variation in the Giant African Snail Lissachatina fulica (Bowdich, 1822) in its invasive ranges of Asia and West Africa

The rapidly spreading Giant African Snail Lissachatina [=Achatina] fulica (Bowdich, 1822) has been introduced to many parts of the world since the 1800s and is one of the world’s most invasive species. We compared cytochrome oxidase subunit I (COI) sequences from four invasive ranges: India, United Arab Emirates (UAE), China and West Africa. Sixteen distinct haplotypes were identified, with nine found in India, four in the UAE, one in China and four in West Africa. Haplotype 5 was the most common haplotype in Asia and haplotype 1 the most common in West Africa. Network analysis suggests that all haplotypes in India, the UAE, China and West Africa were derived from the most common haplotype 5 which is present in all three invasive ranges in Asia. Higher levels of genetic variation were observed in the invasive ranges of Asia than in West Africa. The high genetic variation observed in Asia, together with high levels of trade as exemplified by wood import data, supports the hypothesis that there could have been multiple invasion events in India and the UAE. Additional sampling from the native and invasive ranges in Africa and from other regions of invasion is essential for understanding the movement and spread of L. fulica.

Unique haplotypes of cacao trees as revealed bytrnH-psbAchloroplast DNA

Cacao trees have been cultivated in Mesoamerica for at least 4,000 years. In this study, we analyzed sequence variation in the chloroplast DNAtrnH-psbAintergenic spacer from 28 cacao trees from different farms in the Soconusco region in southern Mexico. Genetic relationships were established by two analysis approaches based on geographic origin (five populations) and genetic origin (based on a previous study). We identified six polymorphic sites, including five insertion/deletion (indels) types and one transversion. The overall nucleotide diversity was low for both approaches (geographic = 0.0032 and genetic = 0.0038). Conversely, we obtained moderate to high haplotype diversity (0.66 and 0.80) with 10 and 12 haplotypes, respectively. The common haplotype (H1) for both networks included cacao trees from all geographic locations (geographic approach) and four genetic groups (genetic approach). This common haplotype (ancient) derived a set of intermediate haplotypes and singletons interconnected by one or two mutational steps, which suggested directional selection and event purification from the expansion of narrow populations. Cacao trees from Soconusco region were grouped into one cluster without any evidence of subclustering based on AMOVA (FST= 0) and SAMOVA (FST= 0.04393) results. One population (Mazatán) showed a high haplotype frequency; thus, this population could be considered an important reservoir of genetic material. The indels located in thetrnH-psbAintergenic spacer of cacao trees could be useful as markers for the development of DNA barcoding.