Week 1 - Genetics Flashcards by Moyad Safadi

Name 4 examples of Autosomal Dominant inherited diseases

1) Achondroplasia
2) Huntington’s disease
3) Inherited Colon and Breast cancer
4) NF1

How well did you know this?

Not at all

Perfectly

Define:

Variable expression

Variation in severity of a genetic disorder in individuals with the same mutation.

How well did you know this?

Not at all

Perfectly

Define:

Penetrance

Frequency of phenotypic expression of genotype. (or the chance of developing the disease if you have the mutation)

How well did you know this?

Not at all

Perfectly

Define:

Modifier gene

Genes that can affect penetrance and severity of condition in a individual (FGFR2 variants on BRCA2).

How well did you know this?

Not at all

Perfectly

AD inheritance:

what is the pattern of inheritance?

Vertical, effecting both males and females.

How well did you know this?

Not at all

Perfectly

Name 2 examples of Autosomal Recessive inherited diseases

1) Cystic fibrosis

2) Sickle Cell Anemia

How well did you know this?

Not at all

Perfectly

AR inheritance:

what is the pattern of inheritance?

Horizontal, effecting both males and females.

How well did you know this?

Not at all

Perfectly

Name 2 examples of X-linked recessive diseases

1) Duchenne muscular dystrophy.

2) Becker’s muscular dystrophy.

How well did you know this?

Not at all

Perfectly

X-linked recessive:

what is the pattern of inheritance?

Knights move, mostly males affected (no male to male transition).

How well did you know this?

Not at all

Perfectly

Name 2 examples of X-linked dominant diseases

1) Vitamin D resistant rickets

2) Rett syndrome

How well did you know this?

Not at all

Perfectly

X-linked dominant:

what is the pattern of inheritance?

Vertical, more commonly seen in females then males (2:1 ratio).

How well did you know this?

Not at all

Perfectly

What 4 things are required for a cell to become cancerous?

1) Avoid apoptosis
2) Insensitivity to anti-growth signalling
3) Bypassing replicative senescence
4) Promotes proliferative signalling

How well did you know this?

Not at all

Perfectly

What are 3 ways Tumour Suppressor genes work?

1) Inhibit progression through the cell cycle (TP52, APC)
2) Promote apoptosis (TP53, BAX)
3) Act as a stability gene (BRCA1/2, HNPCC)

How well did you know this?

Not at all

Perfectly

how do Proto-oncogenes function?

Promote cell division by stimulating the cell cycle

How well did you know this?

Not at all

Perfectly

How do Proto-oncogene mutations lead to its tumourgenic effect?

Is called Oncogene when mutated
When it mutates it “gains function” leading to over proliferation of cells
Only one copy required for tumorgenic effect
Not usually inherited

How well did you know this?

Not at all

Perfectly

How do Tumour Suppressor Gene Mutations lead to its tumourgenic effect?

When it mutates it is a “loss of function” that leads to tumorgenic effect
Requires two inactivated gene copies for tumorgenic effect

How well did you know this?

Not at all

Perfectly

How do Stability Genes function?

Minimise genetic alterations by acting as DNA repair genes.

How well did you know this?

Not at all

Perfectly

What are 3 features of familial cancers?

1) Uncommon
2) Early onset
3) Multiple primary tumours

How well did you know this?

Not at all

Perfectly

What are 3 features of Sporadic (non-inherited) cancers?

1) Common
2) Late onset
3) Single primary Tumour

How well did you know this?

Not at all

Perfectly

What is Genetic Anticipation?

The number of Mutations (specifically repeating codes) increases with each generation
Leading to increasing severity and earlier onset in successive generations.

How well did you know this?

Not at all

Perfectly

Name 3 Diseases with Genetic Anticipation?

1) Huntington’s (CAG)
2) Fragile X syndrome
3) Myotonic Dystrophy (CTG)

How well did you know this?

Not at all

Perfectly

What is Pseudo-dominant inheritance?

A Autosomal Recessive condition that looks Autosomal Dominant due to high carrier frequency

How well did you know this?

Not at all

Perfectly

What is Mitochondrial inheritance?

Mitochondria has its own genome which we inherit from our mothers
Mutations lead to syndromes that often affect eyes, muscles and brain (e,g, Leigh’s disease)

How well did you know this?

Not at all

Perfectly

What is the mode of inheritance in Huntington’s disease?

Autosomal Dominant with genetic anticipation

How well did you know this?

Not at all

Perfectly

What are the symptoms of Huntington's disease?

1) Involuntary movements (Chorea) 2) Dementia 3) Psychiatric problems 4) Underweight due to dysphagia

What is the Genetic mutation associated with Huntington's disease?

- Repetition of CAG codon in the HTT gene | - Over 40 repetitions needed for disease

What is the mode of inheritance in Myotonic Dystrophy?

Autosomal Dominant with genetic anticipation

What are the symptoms of Myotonic Dystrophy?

1) Progressive muscle weakness 2) Inability to relax muscles after effort (myotonia) 3) Cataracts

What is the Genetic mutation associated with Myotonic Dystrophy?

- Repetition of CTG codon in the DMPK gene | - Over 50 repeats needed for disease

What is the mode of inheritance in Cystic Fibrosis?

Autosomal Recessive

What are the symptoms of Cystic Fibrosis?

1) Recurrent lung infection 2) Exocrine pancreas insufficiency 3) Bronchiectasis 4) Male infertility

What is the Genetic mutation associated with Cystic Fibrosis?

- F508 deletion on the CTFR gene (deletion of Pheylalanine) | - In frame deletion (only one AA effected)

How do you diagnose Cystic Fibrosis?

1) Screen newborns blood for immunoreative trypsin (raised in CF) 2) DNA testing 3) sweat testing for raised Cl- ions

What is the Genetic mutation associated with Down Syndrome?

Trisomy 21

What are the signs and symptoms of Downs Syndrome?

1) Learning difficulties 2) Congenital heart malformations 3) Hypothyroidism

What is the Genetic mutation associated with Edwards Syndrome?

Trisomy 18

What are the signs and symptoms of Edwards Syndrome?

1) Small chin 2) Learning disabilities 3) Overlapping fingers 4) Organ malformation

What is the Genetic mutation associated with Patau syndrome?

Trisomy 13

What are the signs and symptoms of Patau Syndrome?

1) Micropthalmia 2) Abnormal ears 3) Cleft lips and palate 4) post axial polydactyly (extra pinky) (don't remember the fancy name)

What mutations are commonly associated with an increased risk of breast cancer?

1) BRCA1 2) BRCA2 3) TP53 4) PTEN

What type of genes are BRCA?

- Stability genes | - The function is DNA repair by homologous recombination of double stranded breaks

What mutations are commonly associated with an increased risk of Ovarian cancer?

1) BRCA1 2) BRCA2 3) HNPCC genes (MLH 1/2) 4) RAD51C

What is the target of the Pharmacological treatment of ovarian cancer?

- PARP inhibition (Olaparib) - Cancer cells with BRCA1 mutations rely on PARP (another gene) to replicate, therefore by inhibiting this pathway the cancer cells cannot replicate.

What are the 3 familial (inherited) colon cancers?

1) Hereditary Non-Polyposis Colorectal Cancer (Lynch syndrome or HNPCC) 2) Familial adenomatous polyposis 3) MYH polyposis

What mutations are associated with Hereditary Non-Polyposis Colorectal Cancer?

1) MLH1 2) MSH2 3) MSH6

What are class of genes do MLH1, MSH2 and MSH6 belong to?

DNA mismatch repair genes

What other organs are at risk of developing polyps in patients with HNPCC?

1) Uterus 2) Stomach 3) Ovaries

What mutation is associated with Familial Adenomatous Polyposis (FAP)?

Mutation of the APC gene on chromosome 5

What is Familial Adenomatous Polyposis (FAP)?

It is a AD inherited predisposition for colorectal cancers, patients may initially have large numbers of benign polyps in the colon that can become malignant.

What is MYH polyposis?

It is a mild form of FAP that is AR, presents with less colon polyps and has a lower chance of becoming malignant then FAP.

What mutation is associated with MYH polyposis?

Mutation of the BER (base excision repair gene)

What is Li Fraumeni Syndrome?

It is an autosomal dominant cancer predisposition syndrome

Name 4 cancers that Li Fraumeni Sydrome predisposes?

1) Breast cancer 2) Brain tumours 3) Sarcoma 4) Leukaemia

What is the mode of inheritance in Neurofibromatosis 1 (NF1)?

Autosomal Dominant

What are the symptoms of Neurofibromatosis 1 (NF1)?

1) flat pigmented birth marks (Cafe au lait macules) 2) Benign skin and nerve sheath tumours (neurofibromas) 3) Short stature 4) Macrocephaly

What is the Genetic mutation associated with Neurofibromatosis 1 (NF1)?

NF1 gene (a TSG gene)

What is the mode of inheritance in Duchenne's Muscular Dystrophy?

X-linked recessive

What are the symptoms of Duchenne's Muscular Dystrophy?

- Early onset of symptoms ~ 3yrs old - Delayed walking - Progressive muscle weakness

What is the Genetic mutation associated with Duchenne's Muscular Dystrophy?

Out of frame deletion on the DMD gene, this gene is responsible for coding the protein Dystrophin that is required for muscle formation.

What is the mode of inheritance Becker's Muscular Dystrophy?

X-linked recessive

What are the symptoms of Becker's Muscular Dystrophy?

- Early onset of symptoms ~ 12yrs old - Delayed walking - Progressive muscle weakness - Less severe then Duchennes

What is the Genetic mutation associated with Becker's Muscular Dystrophy?

In frame deletion on the DMD gene

What is the mode of inheritance in Fragile X Syndrome?

X-linked recessive with genetic anticipation

What are the symptoms of Fragile X Syndrome?

Most common inherited cause of significant learning disabilities

What is the Genetic mutation associated with Fragile X Syndrome?

CGG repeating codons in the FMR1 gene

What chromosomal abnormality is found in Turner Syndrome?

Only one X sex chromosome in females (X)

What chromosomal abnormality is found in Kleinfelters Syndrome?

An additional X sex chromosome in males (XXY)

What 2 techniques would you use to detect an unknown point mutation?

1) Sanger sequencing | 2) Massively parallel sequencing

What technique would you use to detect a known point mutation?

Allele Specific PCR (ARMS)

What technique would you use to detect unknown duplication's or deletions?

Array Competitive Genomic Hybridisation (aCGH)

What technique would you use to detect known duplication's or deletions?

MLPA-PCR

What 3 techniques would you use to detect Aneuploidies?

1) Quantitative fluorescent PCR (QF-PCR) 2) Karyotyping (light microscope) 3) Fluorescence in situ hybridization (FISH)