Genome sequencing Flashcards
What is the significance of the completion of the Human Genome Project?
The completion of the Human Genome Project provided a complete blueprint of human DNA, revolutionizing human biology by enabling the identification of disease genes, development of gene therapies, and a deeper understanding of human health and disease.
Explain the concept of ‘positional cloning’ and why it was a challenging technique in human genetics.
Positional cloning was a laborious and time-consuming technique used to identify genes based on their location on chromosomes. It involved using genetic markers and linkage analysis to narrow down the region containing the gene of interest, making it a challenging process before the availability of the human genome sequence.
Why is it crucial to sequence the DNA of both parents and the affected child when investigating a de novo mutation?
Sequencing the DNA of both parents and the affected child allows researchers to identify mutations specific to the child. By comparing the child’s DNA to the parents’, variants inherited from the parents can be ruled out, increasing the chances of finding the disease-causing de novo mutation.
What are the key characteristics of rare diseases, and how has genome sequencing impacted their understanding and diagnosis?
Rare diseases are individually uncommon, affecting less than 1 in 2000 people, but collectively affect a significant portion of the population. Genome sequencing has revolutionized their diagnosis by enabling the identification of causative genes, leading to a better understanding of these disorders and fostering connections between affected families worldwide.
Describe the mechanism of action of Nusinersen in treating Spinal Muscular Atrophy (SMA).
Nusinersen is an oligonucleotide drug that targets the SMN2 gene, promoting the inclusion of exon 7 during splicing. This results in increased production of functional SMN protein, which partially compensates for the deficiency caused by mutations in the SMN1 gene in SMA patients.
Explain how the understanding of hereditary persistence of foetal haemoglobin (HPFH) has led to therapeutic strategies for sickle cell disease.
Individuals with HPFH continue to produce foetal haemoglobin throughout their lives. Clinical observations revealed that sickle cell disease patients with co-existing HPFH experienced milder symptoms, indicating that foetal haemoglobin could compensate for the defective adult haemoglobin. This led to therapeutic strategies targeting the reactivation of foetal haemoglobin production in sickle cell disease.
How has transcriptome sequencing, particularly single-cell sequencing, advanced our understanding of diseases like medulloblastoma?
Transcriptome sequencing, specifically single-cell sequencing, has allowed researchers to analyze gene expression profiles of individual cells within a tumor. In medulloblastoma, this revealed four distinct subtypes with different underlying genetic causes, providing valuable insights into tumor heterogeneity and potential therapeutic targets.
What are Genome-Wide Association Studies (GWAS), and what are their limitations in understanding complex genetic disorders?
GWAS are large-scale studies that compare genomes of individuals with and without a particular disease to identify genetic variations associated with the disease. However, they often identify many common variants with small effects, making it difficult to pinpoint specific causative genes and understand the complex interplay of genetic and environmental factors in these disorders.
Describe the role of biobanks in studying the interplay of genetics and environmental factors in complex diseases.
Biobanks are large-scale repositories of biological samples and health information from a diverse population. By combining genetic data, health records, and lifestyle information, they provide a powerful tool for studying the complex interplay of genes and environment in the development of diseases like heart disease, diabetes, and cancer.
How has genome sequencing contributed to our understanding of infectious diseases, specifically focusing on COVID-19?
Genome sequencing of the SARS-CoV-2 virus allowed for rapid development of diagnostic tests and vaccines. Additionally, GWAS on COVID-19 patients identified genetic variations associated with disease severity, providing insights into the host factors influencing susceptibility and immune responses to the infection.
