Introduction - the basics Flashcards
What is molecular genetics?
The study of structure and function of individual genes.
What is clinical genetics?
The application of genetics to diagnosis and patient care.
How are genetic disorders tested for?
Cytogenetics MLPA tests Karyotype X-rays Blood tests ...
What mutations in genes involved with ENaC (Na channels) lead to?
Hypertension.
-involved in renal salt balance
Mutations in what genes are associated with type 1 diabetes?
Glucokinase transcription factors.
-pancreatic beta cells
What gene mutations are associated with idiopathic epilepsy and migraines?
Ion channels.
-e.g. KCNj10
What can ASPM gene mutations lead to?
Abnormal head size.
-e.g. microcephaly
Name some genes associated with monogeneic autoimmune disorders.
AIRE
TREX1
RNAseH2
What is a Gefitinib?
1st selective inhibitor of EGFR.
- used to treat certain cancers (e.g. NSCLC)
- more effective in some patients
- France screen patients for EGFR mutations
What’s the difference between pharmacogenomics and pharmacogenetics?
PHARMACOGENOMICS - analysing entire genomes (groups of people) to identify genetic factors influencing drug responses
-more population based
PHARMACOGENETICS - studying individual’s genetics to predict drug responses
-more individual based
What is Gleevec used to treat?
Chronic myeloid leukaemia (CML).
What genetic mutation causes chronic myeloid leukaemia?
Translocation (9;22).
What is the fusion gene called in chronic myeloid gene?
BCR/abl gene.
- abl gene (chr 9)
- BCR gene (chr 22)
What chromosome contains the BCR/abl gene in chronic myeloid leukaemia?
Philadelphia chromosome.
-chr 22
What are the main 3 categories that contribute to the aetiology of disease?
- Environment
- Single gene
- Polygenic
What causes achondroplasia (dwarfism)?
Single gene mutation.
-FGFR3
What is the main similarity between the following:
- Duchenne muscular dystrophy
- Haemophilia
- Phenylketonuria?
Mainly caused by genetics rather than environment.
What is the main similarity between the following:
- Scurvy
- TB?
Mainly caused by environment rather then genetics.
What does multifactorial / complex mean?
Interaction of multiple genes and environmental factors.
-e.g. type II diabetes, IHD
What type of genetic disorders have Mendelian inheritance?
Single gene disorders.
What is a chromosomal genetic disorder?
Imbalance / rearrangement in chromosomal structure.
Give examples of chromosomal mutations. (3)
- Aneuploidy
- Deletion
- Translocation
What are somatic mutations?
Mutations within a gene in a defined population of cells that results in disease.
-e.g. breast cancer
What are the main single gene modes of inheritance? (4)
- Autosomal dominant
- Autosomal recessive
- X-linked
- Mitochondrial
What structures does autosomal dominant inheritance normally affect? (3)
- Structural proteins
- Receptors
- Transcription factors
What is the main similarity between Marfans and Huntington disease?
Both autosomal dominant inheritance.
What is penetrance?
The frequency that a genotype is expressed by those individuals that possess it (%).
Give an example of penetrance altering with age.
Huntington disease.
-100% penetrance by 80yrs
What is incomplete penetrance?
When not all relatives who inherit the mutation develop the disorder.
(e.g. BRCA1»_space; breast cancer)
What is expressivity?
Variation in expression.
-the extent to which a heritable trait is present
What is anticipation?
Symptoms of a genetic disorder becoming apparent at an earlier age (and more severe) as passed from one generation to the next.
-e.g. Huntington’s
When does a new dominant / de novo mutation occur?
During gametogenesis / early embryonic development.
Can de novo mutations be passed on?
Yes, parents of the affected individual do not have them, but they can be passed on to offspring.
What can increase the risk of autosomal recessive inheritance?
Consanguineous relationship.
Name some disorders with autosomal recessive inheritance. (4)
- Cystic fibrosis
- Haemachromatosis
- Sickle cell disease
- Metabolic disorders
Can you have male-male transmission of X-linked disorders?
No.
Name some disorders with X-linked inheritance. (4)
- Duchenne musclar dystrophy
- Fragile X syndrome
- Haemophilia
- Red/green colour blindness
What are the outcomes is the mother is a carrier of an X-linked disorder?
25% normal girl
25% carrier girl
25% normal boy
25% affected boy
What are the outcomes is the father is a affected with an X-linked disorder?
- All daughters are carriers
- All sons are unaffected
What are the 2 main factors influencing phenotype of female X-linked disorder carriers?
- X inactivation
- XL dominant vs XL recessive inheritance
> > variable phenotype
What is another term for x-inactivation?
Lyonisation.
What is x-inactivation?
Random inactivation of one of the X chromosomes in female cells.
-more than 1 x chromosome
When does x-inactivation occur?
Early embryogenesis.
-remains inactive throughout lifetime of cell
How can x-inactivation affect x-linked female carriers?
Inactivation of normal X chromosome»_space; significant phenotype.
-e.g. fragile X syndrome
What is Rett syndrome?
Disorder of brain development.
- X linked dominant
- lethal in males, phenotype only in females
Give 2 examples of mitochondrial inheritance.
Maternally inherited diabetes and deafness.
How are males and females affected by mitochondrial inheritance?
Males and females affected equally.
How many genes are present in motichondrial DNA?
27 genes.
What is the inheritance pattern of mitochondrial inheritance?
- Affected mother»_space; affected children
- Affected father»_space; unaffected children
FAMILY TREE :
what are the symbols for genders?
Male = square Female = triangle Unspecified = diamond
FAMILY TREE :
what does a double line joining a couple mean?
Consanguineous.
FAMILY TREE :
what does a line through a symbol mean?
Person has died.
FAMILY TREE :
what does a shaded centre mean?
Carrier of x-linked recessive disorder.
FAMILY TREE :
what does a half shaded symbol mean?
Heterozygous for autosomal recessive disorder.
FAMILY TREE :
what does a shaded symbol mean?
Affected individual.
FAMILY TREE :
what is the symbol for a stillborn baby?
Diamond with a line through and SB next to it.
FAMILY TREE :
what is the symbol for a therapeutic abortion?
Triangle with a line through.
FAMILY TREE :
what is the symbol for a spontaneous abortion / miscarriage?
Triangle.
