Genetics in Medicine 1-10

Question 1

True or false: Single gene disorders have a high recurrence rate

Answer 1

True

Question 2

True or false: Environmental diseases are less common than single gene disorders

Answer 2

False

Question 3

What is a somatic mutation genetic disorder?

Answer 3

Mutation within a gene in a defined population of cells that results in disease, e.g. breast cancer

Question 4

Are males or females affected more by autosomal dominant inheritance?

Answer 4

Equally affected

Question 5

What types of proteins are normally affected by autosomal conditions, and name some conditions.

Answer 5

Structural proteins, receptors, transcription factors.

Myotonic dystrophy, Marfan syndomr, Huntington disease

Question 6

What is the definition of penetrance?

Answer 6

The frequency with which a specific genotype is expressed by those that posses it, usually given as a percentage.

Question 7

What is meant by expressivity?

Answer 7

The extent to which a heritable trit is manisfested by an individual - variation in expression.

Question 8

What is the risk of offspring being affected in autosomal recessive inheritance to 2 carrier parents?

Answer 8

1/4

Question 9

Name some conditions with autosomal recessive inheritance

Answer 9

CF
Metabolic disorders
Haemachromatosis
Sickle cell disease

Question 10

Who is affected by X-linked inheritance?

Answer 10

Males, however cannot have male to male transmission

Question 11

Name some conditions with X-linked inheritance

Answer 11

DMD
Fragile X
Red-green colour blindness
Haemophilia

Question 12

What are some of the difficulties with using PCR?

Answer 12

Gene may be too big

GC-rich regions are difficult to PCR - fragile X mutation has repetitive CGG sequence

Question 13

What genetic techniques are used if we already know the identity of the mutation? And if we do not?

Answer 13

PCR

DNA sequencing
Karyotyping

Question 14

Which direction is DNA written in

Answer 14

5’ –> 3’

Question 15

What is satellite DNA?

Answer 15

Large blocks of repetitive sequences, found at centromeres and heterochromatic chromosomal regions

Question 16

What occurs in transcription and translation?

Answer 16

Transcription: DNA –> RNA
Translation: RNA –> protein

Question 17

What is an intron?

Answer 17

Non-coding region

Question 18

What is the difference between SNV and SNP mutations?

Answer 18

SNV = variant, >1%
SNP = polymorphism, <1%

Question 19

What are the definitions of aneuploidy, polyploidy and mosaicism?

Answer 19

Anueploidy = gain or loss of chromosome
Polyploidy = gain entire sets of chromosomes
Mocaism = diploidy (normal 2 copies) and aneuploidy

Question 20

What is non-disjunction in meiosis?

Answer 20

Failure of chromosome / chromatid separation. Some gametes have no genetic material, others have double.

Question 21

What is Trisomy 21? Describe some of the clinical features observed.

Answer 21

Downs syndrome.

Upward slanting eyes, protruding tongue, single palmar crease, wide sandal gap, learning difficulties

Question 22

What is trisomy 18? Descrive the clinical features observed.

Answer 22

Edwards Syndrome.
Microcephaly, low set ears, cleft palate, clenched hands, rockerbottom feet, severe mental retardation, organ malformations e.g. umbilical / inguinal hernia, heart/kidney/eye abnormalities

Question 23

What is trisomy 13? Describe the clinical features.

Answer 23

Patau syndrome.

Small at birth, mental retardation, microcephaly, brain defects, cleft palate, heart defects, abnormal genitalia

Question 24

What are the sex chromosome disorders, 45X and 47XXY?

Answer 24

45X = Turner's syndrome
47XXY = Klinefelter's syndrome

Question 25

Describe some features of Turner's syndrome

Answer 25

Loss of ovarian function, no puberty, webbed neck, swollen hands and feet, coarctation of aorta, reduced IQ`

Question 26

Describe some features of Klinefelter's syndrome

Answer 26

Testicular dysgenesis, 30-50% gynaecomastia, long limbs in adults

Question 27

What is a molar pregnancy?

Answer 27

Double paternal DNA with no maternal. "Conception without an embryo"

Question 28

Summarise which numerical abnormalities occur during: 1) meiosis 2) fertilisation 3) post-fertilisation

Answer 28

1_ gain/loss of single chromosome 2) gain of whole chromosome sets 3) gain or loss during mitosis

Question 29

What is a robertsonian translocation?

Answer 29

Whole arm of chromosome breaks off and fuses with another chromosome

Question 30

What is a chromosome inversion?

Answer 30

Chromosome broken at 2 points, then rejoined. Paricentric: occurs about centromere, pericentric: no centromere involvement

Question 31

What is FISH used for?

Answer 31

Copy number imbalance, aneuploidy, confimration of G-banding and array CGH, identifying specific abnormalities in cancer

Question 32

What is a copy number variation?

Answer 32

DNA segment with variable copy number compared with refernece genome.

Question 33

What is MLPA?

Answer 33

Mulitplex-ligation-dependent-probe-amplification. | Mulitplex PCR, alternative to FISH

Question 34

What is array CGH?

Answer 34

Genome wide screen which sees genomic imbalances at high resolutuion

Question 35

What are the advantages of array cGH?

Answer 35

early diagnosis high reesolution high accuracy information on relevant genes

Question 36

What is a gatekeeper gene?

Answer 36

Cancer gene that monitors and controls cell division and death, preventing accumulation of mutations.

Question 37

What is a caretaker gene?

Answer 37

Cancer gene that improves genomic stability e.g. repair of mutations

Question 38

What is a landscape gene?

Answer 38

Cancer gene that controls the surrounding stroll environment

Question 39

What is a tumour suppressor gene? Name a well-known example.

Answer 39

Suppresses cell growth to protect cells from becoming cancerous. BRCA1/2.

Question 40

What is an oncogene?

Answer 40

Regulates cell growth and differentiation. Activation mutations allows cell growth to become out of control.

Question 41

What is Knudson's two-hit hypothesis? Name the classic example of cancer that demonstrates this.

Answer 41

2 mutations are required within a single cell to cause cancer. However, in inherited disease, one of the mutations already exists, therefore there is a higher risk of cancer as only one further mutation is required. Retinoblastoma

Question 42

Which inheritance patterns do most cancer syndromes follow?

Answer 42

Autosomal dominant

Question 43

Name some features that help to distinguish a familial cancer against a sporadic.

Answer 43

Familial = younger age of inset, FHx of same type / genetically related cancers

Question 44

What is HNPCC, what is its inheritance pattern and what does it hold a risk for?

Answer 44

Hereditary non-polyposis colorectal cancer. 60-80% risk of bowel adenoma, other cancer risks = endometrial/ovarian/stomach/ GUT. Autosomal dominant inheritance

Question 45

What criteria is used to assess whether someone has HNPCC?

Answer 45

Amsterdam

Question 46

What is Li Fraumeni Syndrome?

Answer 46

Mutation in P43 tumour supressor gene. 50% cancer by age 40 = breast, brain, adrenocortex, leukaemia.

Question 47

Inheritance of haemachromatosis

Answer 47

Autosomal recessive

Question 48

Term used to describe the extent to which a heritable trait is manifested by an individual

Answer 48

Expressivity

Question 49

Myotonic dystrophy is inherited in an autosomal _________ fashion

Answer 49

Dominant

Question 50

The classic Fragile X mutation occurs in a tract of sequence which is

Answer 50

Repetitive

Question 51

This drug blocks the abnormal tyrosine kinase activity in cases of chronic myeloid leukaemia which have the classic translocation between chromosomes 9 and 22.

Answer 51

Gleevec (Imatinib)

Question 52

The chromosome that carries the BCR/abl fusion gene is referred to as the _____________ chromosome

Answer 52

Philadelphia

Question 53

Mutations in this gene result in microcephaly

Answer 53

ASPM

Question 54

The condition of diabetes and deafness is ______________inherited

Answer 54

Maternally

Question 55

Small cell lung cancers which harbour EGFR/HER1 mutations can be treated with this drug.

Answer 55

Gefitinib

Question 56

OLA assay stands for?

Answer 56

Oligonucleotide ligation assay

Question 57

Term used to describe the process of random inactivation of one of the X chromosomes in cells with more than one X chromosome

Answer 57

Lyonisation