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Flashcards in Genomic medicine Deck (27):

Situations in which genomic medicine is useful?

• Diagnosis
• Identifying people at increased risk
• Tracking epidemics
• Personalising drug treatments (including cancer)
• Developing new therapies


Three types of gene mutation?

1) Inherited – autosomal/ X-linked recessive/dominant
2) De novo dominant mutation
3) Mosaic mutation


What is a mosaic mutation or mosaicism?

Two or more populations of cells with different genotypes in one individual


Limits to sequencing by synthesis?

• Poor at capturing simple repeats, and GC rich areas
• Misses promoters, UTRs, microRNAs
• Targeted panels may be better


Main principle behind sequencing by synthesis?

Recordign energy given off by marked base pairing


Are mixed race families more or less likely to have the same recessive allele?

Less likely


What is a germline mutation and a somatic mutation?

Germline: is a mutation in an egg or sperm cell itself

Non-germ-line tissue mutation, so can't be inherited


Are many inherited cancers due to oncogenes or tumour suppressant gene mutations?

tumour suppressant


What are DNA repair genes, what could their mutation lead to?

Genes responsible for correcting the mutations in DNA, a mutation in a DNA repair gene can lead to cancer through the propagation of mutated onco/tunour suppressant gene.


Why can next-gen sequencing be difficult in cancers?

• Cancer genomes are complex and diverse
• Most cancers are aneuploid (abnormal chromosome number)
• Limited biopsy DNA
• Whole genome amplification might be needed to identify certain mutations (e.g. fusions)
• Often has necrotic, apoptotic cells in sample
• Formalin can damage DNA
• Tumours can contain normal DNA, tumour DNA, and different tumour clones


What are driver and passenger gene mutations?

Drivers give the clone a selective advantage and contribute to oncogenesis

Passengers have no effect on clone survival


Why would next-gen sequencing be useful in cancer?

Identify the exact gene mutations causing the cancer


What is minimal residual disease and how is this useful in cancer?

measures the proportion of tumour cells with a defining mutation

e.g. If the ratio of allele A:allele B is no longer 50:50 then this suggests a loss of heterozygosity, therefore clonal expansion, therefore cancer


Use of minimal residual disease testing in cancer?

- Prognosis
- Quantifying drug response
- Monitoring remission and relapse
- Guiding treatment


What is SCID?

Severe combined immunodeficiency


What are PIDs?

Primary immune deficiency


Some treatments for PIDs?

Folinic acid

bone marrow transplant


Types of next generation sequencing (NGS)?

Whole genome sequencing

Whole exome sequencing

Targeted gene panels


What percentage of disease causing variants are in the exome?



What are SNIPS?

Single nucleotide polymorphisms

Heterozygous - different


How much roughly would it cost to have your genome sequenced now?

About £1000


Problems when not doing whole genome sequencing?

Simple repeats are poorly captured

Whole exome is not the WHOLE exome - some will be missing

Clinical exome evolves over time


Best choice in individuals to sequence if a child has a genetic disease to find the cause?

Either closely related and unaffected individuals

Or distantly related affected individuals


What is tiered analyses?

When you have a patient with a specific condition and you first look at the genes we know are involved in that condition


How can you filter data?

Tiered analysis

Mode of inheritance e.g. it's X linked so look at things only on X

Synonymous variants - codes for the same amino acid

Look specifically at things we know make a big difference e.g. like Frameshifts, stop codon.

Concordant variants - if the mutation is seen in unaffected individuals it can be discarded

Conservation metrics - whether it has been the same in evolution


What is the genomics england programme?

Sequence rare disease and cancer patients

Put it behind a safe firewall

Allow access from selected individuals who can then feed back into treatment/drug design


What is JMML what mutations are associated with it?

Germline CBL mutations