Genetic Basis of Disease

Question 1

What did Garrod do

Answer 1

founder of human biochemical genetics

Question 2

What causes alkaptonuria

Answer 2

defect in enzyme homogentisate 1,2 deoxygenase

Question 3

What are the symptoms of Alkaptonuria

Answer 3

kidney stones, black urine, joint pain

Question 4

How is alkaptonuria inherited

Answer 4

autosomal recessive

Question 5

Name some metabolic inborn errors

Answer 5

cystinuria, phenylketonuria, albinism

Question 6

What did Bateson do

Answer 6

Worked with punnet square to catalogue human disorders

Question 7

Name the Mendelian patterns of inherited human disease

Answer 7

autosomal recessive, autosomal dominant, X-linked

Question 8

Name some autosomal recessive diseases

Answer 8

alkaptonuria, cystic fibrosis

Question 9

Name some autosomal dominant diseases

Answer 9

brachydactyly, huntingtons

Question 10

Name some X-linked diseases

Answer 10

Duchenne muscular dystrophy, haemophilia, X-linked mental retardation

Question 11

Who mainly inherits X-linked disease and why

Answer 11

males - only one X chromosome

Question 12

What mutation causes sickle cell anaemia

Answer 12

single point missense mutation - beta subunit

Question 13

What is the effect of sickle cell anaemia on RBCs

Answer 13

causes misshaping & forming of large insoluble polymers

Question 14

What type of mendelian inheritance is Sickle cell anaemia

Answer 14

Co-Dominance

Question 15

What is an advantage of being heterozygote for sickle cell anaemia

Answer 15

resistant to malaria

Question 16

Example of Co-Dominance

Answer 16

sickle cell anaemia, AB blood type

Question 17

Examples of incomplete dominance

Answer 17

pink snapdragon

Question 18

Describe co-dominance

Answer 18

heterozygotes express both alleles simultaneously without any blending

Question 19

Describe incomplete dominance

Answer 19

both alleles are partially expressed – intermediate phenotype

Question 20

How is anirida inherited

Answer 20

autosomal dominant

Question 21

What causes Anirida

Answer 21

deletion or loss of function point mutations in one copy of the gene

Question 22

What chromosome does anirida effect

Answer 22

chromosome 11

Question 23

What is the symptom of anirida

Answer 23

lack of an iris

Question 24

What does karyotyping enable

Answer 24

genes to be mapped to specific chromosomal locations

Question 25

How did karyotyping allow identification of disease

Answer 25

abnormalities in banding patterns due to mutations could be recognised

Question 26

How is Duchenne muscular dystrophy inherited

Answer 26

X-linked

Question 27

What chromosome is affected by Duchenne muscular dystrophy

Answer 27

chromosome X

Question 28

What are the symptoms of Duchenne muscular dystrophy

Answer 28

progressive muscle damage and wasting disease

Question 29

What protein is affected by Duchenne muscular dystrophy

Answer 29

Dystrophin

Question 30

What is the function of dystrophin

Answer 30

crucial for muscle integrity

Question 31

What does dystrophin connect

Answer 31

muscle fibres to ECM

Question 32

How is Huntington's disease inherited

Answer 32

autosomal dominant

Question 33

Describe Huntington's disease

Answer 33

progressive neurodegenerative disorder

Question 34

What area of the brain is affected in Huntington's

Answer 34

basal ganglia and lateral ventricles

Question 35

How are the areas of the brain affected in Huntington's

Answer 35

basal ganglia exhibit neuronal loss and lateral ventricles dilate

Question 36

What disease can Huntington's cause

Answer 36

dementia

Question 37

What are the symptoms of huntingtons disease

Answer 37

loss of movement

Question 38

What mutation causes Huntington's

Answer 38

expansion of repeat sequence of CAG

Question 39

What does expansion of repeat sequence of CAG cause

Answer 39

long stretch of glutamine which is toxic to neurons

Question 40

What gene & protein is affected by Huntington's

Answer 40

Huntingtin

Question 41

What causes glutamate expansion

Answer 41

mistakes during DNA synthesis

Question 42

What did Peyton Rous discover

Answer 42

tumour causing virus

Question 43

Describe the genomes of viruses

Answer 43

small and efficient

Question 44

Why does Rous sarcoma virus cause tumours

Answer 44

presence of DNA sequences from the chicken genome

Question 45

What DNA sequences cause tumours in the Rous Sarcoma virus

Answer 45

v-src oncogene

Question 46

What does the v-src oncogene encode

Answer 46

abnormally hyperactive tyrosine kinase

Question 47

What is src

Answer 47

kinase involved with cell proliferation

Question 48

What do viruses contain

Answer 48

oncogenic mutant version of host cellular proto-oncogenes

Question 49

Describe the mutations that give rise to viral oncogenes

Answer 49

dominant, gain of function

Question 50

What causes the philadelphia chromosome

Answer 50

recombination between chromosome 22 and 9

Question 51

What genes fuse in the philadelphia chromosome

Answer 51

BCR & ABL

Question 52

What is the effect of fusion between BCR & ABL

Answer 52

lack of regulation of ABL

Question 53

What is ABL

Answer 53

potential oncogene

Question 54

What does ABL encode

Answer 54

abnormally hyperactive version of tyrosine kinase

Question 55

What do loss of function mutations in tumour suppressor genes cause

Answer 55

tumour growth

Question 56

Describe non-hereditary retinoblastoma

Answer 56

unilateral

Question 57

Describe hereditary retinoblastoma

Answer 57

bilateral

Question 58

What causes hereditary retinoblastoma

Answer 58

inactivation of both alleles of a tumour suppressor gene

Question 59

What causes non-hereditary retinoblastoma

Answer 59

have to acquire two somatic mutations in the same retinal cell

Question 60

What mutations cause cancer?

Answer 60

dominant, gain of function mutations in proto-oncogenes, recessive lost of function mutations in tumour suppressors

Question 61

What are chronic diseases caused by

Answer 61

multiple genes

Question 62

What are SNPs

Answer 62

single nucleotide polymorphisms

Question 63

What are SNPs used for

Answer 63

mapping genes as DNA markers, genome wide association studies

Question 64

What are single nucleotide polymorphisms

Answer 64

random mutations outside of a gene

Question 65

What are genome wide association studies

Answer 65

studies that compare SNPs from healthy vs diseased individuals

Question 66

What is the Manhattan plot

Answer 66

summarises results of GWAS for SNPs associated with disease

Question 67

What are genomic imprints

Answer 67

structural modifications to specific genes - prevent transcription

Question 68

How are DNA methylation patterns re-applied

Answer 68

pattern dependant on sex of embryo

Question 69

What is a hallmark of imprinted chromatin

Answer 69

methylation on cytosine bases in CpG dinucleotides

Question 70

What does imprinted chromatin do

Answer 70

switches genes OFF

Question 71

How does imprinted chromatin switch genes off

Answer 71

recruits transcriptional repressors

Question 72

How do we inherit an imprinted gene

Answer 72

inherit only one working copy of the gene

Question 73

What imprint does UBE3A carry

Answer 73

paternal imprint

Question 74

What imprint does SNORD116 carry

Answer 74

maternal imprint

Question 75

When are imprints created

Answer 75

gametogenesis

Question 76

When are imprints erased

Answer 76

embryonic precursors of germ cells during embryonic development

Question 77

When are imprints re-established

Answer 77

spermatogenesis/oogenesis depending on sex of offspring

Question 78

What causes Angelman syndrome

Answer 78

mutation in UBE3A

Question 79

What are the symptoms of Angelman syndrome

Answer 79

cognitive disability, sleep disturbance, smiling, seizures

Question 80

What causes Prader-willi syndrome

Answer 80

Mutation in SNORD116

Question 81

What are the symptoms of Prader-Willi syndrome

Answer 81

cognitive disability, obesity, hunger, low muscle tone

Question 82

What is the term for impacts of genomic imprint

Answer 82

parent-of-origin specific