Genome seq- Lucky dip Flashcards
What is the main advantage of using genomic sequencing to diagnose rare disorders in children?
Early diagnosis and treatment can have lifelong benefits.
What is the Deciphering Developmental Disorders (DDD) study?
A large-scale sequencing study that investigated over 13,500 families with children who have severe developmental disorders.
What are the two main types of genomic sequencing, and what are their pros and cons?
Exome sequencing:
Pro: Less expensive than whole-genome sequencing.
Con: Only covers protein-coding regions of the genome.
Whole-genome sequencing:
Pro: Highest diagnostic yield.
Con: Most expensive approach.
What is the impact of family structure on the diagnostic yield of genomic sequencing?
Recruitment in a parent-offspring trio significantly increases the probability of diagnosis. This is because it helps identify de novo variants, which are mutations present in the child but not the parents.
Name three factors that might decrease the likelihood of a child receiving a diagnosis through genomic sequencing.
Premature birth
In utero exposure to antiepileptic drugs
Mothers with diabetes
What guidelines are commonly used for classifying genetic variants based on their potential to cause disease?
The ACMG-AMP guidelines.
Why is a thorough clinical workup still crucial for interpreting genetic variants and making a diagnosis?
Clinical evaluation helps determine if a patient’s symptoms align with the expected effects of a specific genetic variant.
It helps rule out other potential causes of the patient’s condition.
What online platform supports the diagnosis of developmental disorders by linking phenotypic and genotypic data?
DECIPHER.
In the DDD study, how was the potential for overlooking causal variants addressed in the diagnostic pipeline?
The pipeline incorporated multiple analyses to identify missing variants. Additionally, ‘pathogenic’ or ‘likely pathogenic’ variants in ClinVar and various types of de novo variants were specifically searched for.
What was the role of the DDG2P database in the DDD study?
The DDG2P database contained genes associated with developmental disorders. Variants overlapping these genes were selected for clinical reporting if they met specific criteria like rarity and appropriate zygosity.
How were candidate variants evaluated in the DDD study before being reported to regional genetics teams?
A central clinical review panel assessed the analytic and clinical validity of the candidate variants before reporting them to regional genetics teams via DECIPHER.
Why is informed consent crucial in genomic research?
Participants need to understand the risks and benefits of the study.
They have the right to withdraw at any time.
What are some of the ethical challenges associated with sharing genomic data?
Difficulty in truly anonymizing genomic data
Balancing the benefits of data sharing with the potential risks to participant privacy
How did the DDD study address ethical considerations related to parental DNA samples?
The study aimed to balance the scientific benefit with clinical concerns about genetic information and data management.
Parents were informed that their data would only be used to understand their child’s disorder.
Potential safeguarding issues were flagged to the referring clinical team.
What are some of the benefits of receiving a genetic diagnosis for a rare disorder?
Better understanding of prognosis
More tailored management and improved surveillance
Accurate genetic counseling and increased reproductive choice
Access to support groups
