Related Experiment Video
Updated: Aug 15, 2026
06:59
Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter
Published on: March 31, 2022
Haplotype diversity and somatic instability in normal and expanded SCA8 alleles
Sandra Martins1, Ana I Seixas, Paula Magalhães
1UnIGENe, IBMC, Universidade do Porto, Portugal.
Summary
Spinocerebellar ataxia type 8 (SCA8) expansions arose in common genetic backgrounds in Portuguese families. This region of the SCA8 gene exhibits instability beyond the repeat sequence, impacting disease penetrance.
Area of Science:
- Genetics
- Neurodegenerative Diseases
- Molecular Biology
Background:
- Spinocerebellar ataxia type 8 (SCA8) is a late-onset neurodegenerative disorder caused by trinucleotide repeat expansions.
- SCA8 presents challenges due to reduced penetrance, repeat instability, and an unclear functional role of the (CTA)n(CTG)n expansion.
Purpose of the Study:
- To investigate the genetic background and molecular characteristics of the (CTA)n(CTG)n repeat expansion in Portuguese families with SCA8.
- To analyze haplotype diversity and identify sequence variations within the SCA8 gene region.
Main Methods:
- Haplotype and sequencing analysis were performed on four SCA8 families and 20 control families.
- Cloning and sequencing of normal, unstable normal, and expanded SCA8 gene fragments were conducted.
Main Results:
- Two primary haplotypes, AG-Exp-GTTG and AG-Exp-CTTG, were identified in SCA8 families and were also frequent in controls.
- Eleven distinct base substitutions were found in exon A of the SCA8 gene.
- Somatic variability in repeat size and base composition was observed in both normal and expanded chromosomes.
Conclusions:
- SCA8 expansions in Portuguese populations originated from common ancestral backgrounds.
- The region surrounding the (CTA)n(CTG)n repeat in the SCA8 gene is inherently unstable, extending beyond the repeat itself.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
01:20Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...