![]() We refer to variants corresponding to pseudogene bases in this region as GBAP1-like. Pathogenic missense changes in the high homology exon 9–11 region such as the common p.L483P (NC_000001.11:g.155235252 A > G, also known as p.L444P) may arise by gene conversion, rather than simple base substitutions, with pseudogene sequence incorporated into the gene 7. The SV variability and population prevalence remain largely unknown. These include CNLs outside the coding region, and all CNGs, which consist of a partial duplication of pseudogene sequence merged with a variable part of the gene, often only the 3′ UTR, with the resulting allele still containing a normal copy of the GBA coding region (Fig. Conversely, SVs not affecting the coding sequence are not pathogenic, although a modifier effect cannot be excluded 7. SVs that disrupt the coding sequence by gene conversion or reciprocal recombination are expected to be pathogenic for GD and risk factors for PD. ![]() Throughout this paper, we use the term copy number gain (CNG) for reciprocal duplication alleles where a 20.6 kb long region of DNA between the homology segments of GBA and GBAP1 is multiplied, and copy number loss (CNL) for reciprocal fusion alleles where the same region is deleted, creating GBA- GBAP1 fusions 7 (see Fig. These can be non-reciprocal, also termed gene conversion, or reciprocal, resulting in copy number variants (CNV). The high homology predisposes to non-allelic homologous recombination between GBA and GBAP1, leading to a wide range of structural variants (SV) 7. This rises to 98% in the region from intron 8 to the 3′-UTR, where there are five identical segments >200 bp each 6. Identifying GBA mutations is difficult due to a pseudogene ( GBAP1) located 6.9 kb downstream 5 which has an overall homology of 96% with GBA. Heterozygous variants in GBA are associated with an increased risk of developing Parkinson's disease (PD) 3, the second most common neurodegenerative disease, and the closely related Lewy body dementia (LBD) 4. Around 500 disease-causing mutations have been reported, mostly missense changes arising from single nucleotide variants (SNVs) 2. The GBA gene encodes the lysosomal enzyme glucocerebrosidase, and biallelic mutations in GBA cause the autosomal recessive disorder Gaucher disease (GD ) 1. These findings highlight the importance of accurate GBA analysis in these patients. Gauchian detects more GBA variants in LBD than PD, especially severe ones. Gains may coexist with other mutations in patients, and a modifying effect cannot be excluded. CNV frequencies in PD and LBD are similar to controls. Applying Gauchian to sequencing of over 10,000 individuals shows that copy number variants (CNVs) spanning GBAP1 are relatively common in Africans. Both methods were concordant for 42 samples carrying a range of recombinants and GBAP1-related mutations, and Gauchian outperformed the GATK Best Practices pipeline. ![]() We present two methods to resolve recombinant alleles and other variants in GBA: Gauchian, a tool for short-read, whole-genome sequencing data analysis, and Oxford Nanopore sequencing after PCR enrichment. The presence of pseudogene GBAP1 predisposes to structural variants, complicating genetic analysis. Alternatively, this content might fit in r/gamecollecting.GBA variants carriers are at increased risk of Parkinson’s disease (PD) and Lewy body dementia (LBD). Provide a prompt with your post for discussion as body text within the post itself. Collection/pickup posts may be posted on Saturday and Sunday. Use Pricecharting or similar pricing services, or eBay sold listings for a method of determining the value of your games, consoles or paraphernalia.Ĭollection/Pickup Posts. Because live streams expire, they are not examples of good content for this subreddit and are not allowed. Reddit is a link aggregation service at its core. Adhere to reddiquette and all reddit site-wide rules. Remember that there's a human on the other end of the screen. "Collection," "Battlestation," and "Score" posts may contain modern games, but they must be majority vintage or vintage-focused.ĭon't be a dick. However, discussion about newer platforms is a allowed as discussion, just not as a top-level post. Dreamcast allowed as an honorary 5.5th gen console. r/retrogaming is for posts about vintage gaming: 5th gen platforms and earlier. ![]() For more information please Reddit's self-promotion rules here. (No live streams, though.) However, we ask that your self promotional content not be more than around 10 percent of your total posts. ![]() It's perfectly okay to post your YouTube video, blog, or kickstarter here. This subreddit is reddit's home for vintage gaming. r/retrogames: Our discussion-only sister subreddit ![]()
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