Inheritance of human disease

Question 1

what is penetrance ?

Answer 1

the likelihood of having a disease if you have a gene mutation

Question 2

what level of penetrance is mendelian disorder ?

Answer 2

high penetrance

Question 3

what mendelian inhertance are there ?

Answer 3

autosomal dominant
autosomal recessive
X-linked
mitochondrial

Question 4

what is expression ?

Answer 4

variation in disease severity if you have the mutation

Question 5

what does PCR allow you to do ?

Answer 5

select one small piece of human genome from a patient and amplify it
pieces can be sequenced to find mutations

Question 6

what are the different types of mutations ?

Answer 6

Promotor and splice site sequence changes
Base changing causing amino acid change
Base change causing premature stop codon
Insertion or deletion of bases

Question 7

what can happen when a promoter and splice site sequence changes ?

Answer 7

stop transcription
cause abnormal splicing

Question 8

what can happen when base changing causes amino acid change ?

Answer 8

change in protein sequence
may or may not reduce protein function

Question 9

main points for autosomal dominant

Answer 9

• Disease seen in all generations
• 50% risk of affected child if parent affected
• Disease severity variable
• Males and females equally likely to be affected

Question 10

main points for autosomal recessive

Answer 10

• 2 faulty copies of the gene required to cause
  disease
• Often only one generation affected
• 1 in 4 risk of an affected child if parents are carriers
• Increased likelihood in consanguineous
  (incestuous) families
• Usually causes loss of function

Question 11

main points for X-linked

Answer 11

• Y chromosome almost irrelevant
• Haemophilia
• If mother carrier, 50% chance daughter carrier,
  50% chance male affected
• No male-male transmission

Question 12

main points for mitochondrial

Answer 12

• Mitochondrial DNA contains important genes for
  mitochondrial metabolic pathways and ribosomal
  RNAs
• Inherited almost exclusively maternally
• Point mutations and deletions occur
• has symptoms

Question 13

what are the symptoms of mitochonrdrial

Answer 13

Myopathy
Diabetes
Deafness
Optic atrophy
Stroke like episodes
Encephalitis

Question 14

what are common genetic diseases ?

Answer 14

polymorphism
mendelian disorders
multifactorial disease

Question 15

Polymorphism

Answer 15

• Promotor – less protein
• Exon – change in protein function or no effect

Question 16

Mendelian disorders

Answer 16

• High penetrance
• Small environmental contribution

Question 17

Multifactorial disease

Answer 17

• Genetic change just another risk factor
• Penetrance for any one mutation is low
• Individual genetic factors can be treated the same
  way as other environmental risk factors

Question 18

what are non-mendelian inheritance ?

Answer 18

imprinting
Angelman syndrome
heteroplasmy

Question 19

what does DNA methylation lead to ?

Answer 19

modification of histones which represses transcription

Question 20

imprinting

Answer 20

• Differences in gene expression depending on whether a gene is maternally or paternally inherited
• Specific chromosomal regions contain imprinted genes
• Such regions usually contain both maternally and paternally imprinted genes

Question 21

angelman disease

Answer 21

• Neuro-genetic disorder
  o Developmental delay
  o Intellectual disability
  o Ataxia
  o Epilepsy
  o Happy demeanour
  o Frequent laughing and smiling
• Chromosome 15

Question 22

heteroplasmy

Answer 22

• Different daughter cells contain different proportions of mutant mitochondria
• Severity and nature of phenotype depends on proportion and level of mitochondria and the type of mutation