Genetics

Question 1

why is genetics important

Answer 1

All human traits, in particular diseases, have a genetic component which are usually inherited but can be influenced
Help to understand how the condition develops and how it may respond to treatment
Informs patients and their family of potential inheritance patterns - Genetic Counselling

Question 2

how many chromonsomes foes the normal human genome have

Answer 2

Normal human Genome has 23 Chromosomes – 22 autosomes and 1 pair of sex chromosomes
Genes – sections of a Chromosome which code to make a proteins
Genes – 29% human genome
Reminder – non-coding regions responsible for chromosome structural integrity and regulation
30,000 Genes

Question 3

what is the human genome project

Answer 3

Aim: to determine the human genome and identify the genes that it contains
Began in 1990 and completed in 2003,
Collaborative project between the US, UK, France, Germany, Japan and China
Humans are essentially 99.9% similar
Normal DNA Sequence and note for normal variations which aren’t predicted to have damaging effects

Question 4

what are types of genetic disease

Answer 4

multifactorial

chromosomal

single gene

Question 5

example of a single gene mutation

Answer 5

oca2 gene

Question 6

what does the 0ca2 gene do

Answer 6

What does OCA2 gene do?
It gives instruction for a protein called P Protein and are located in melanocytes which produce melanin (pigmentation).
Where is the OCA2 gene?
OCA2 gene is on chromosome 15
What can happen?
If there is a change in the genetic code (Base pairs G-C/A-T) this can effect the instructions given to the enzyme. Sometimes these are physiological which can code for eye colour and some of these changes are pathological changes which leads to significant reduction in pigmentation

Question 7

what condition is caused by 0ca2

Answer 7

albinism - single amino acid and change in gene called oca2

Question 8

what are the types of chromosomal mutations

Answer 8

Change in the number or structure:
- Aneuploidy: - abnormal number of Chromosomes
- Normal Human Genome has 46 Chromosomes
- Can be significantly more detrimental than single gene mutations.

Question 9

what is an eeg of chromosomal mutations

Answer 9

addition of of one of the chromosomes

Question 10

what is the difference between phenotypes and genotypes using eg of albinism

Answer 10

Geneotype – Genetic make up of the individual (i.e. OCA2)
Phenotype – observable characteristics of the individual (i.e. Albinism)
Variability – Penetrance of the Mutation:
1) Other factors influence expression of gene
A) Age-related cumulative frequency
B) Environmental factors
C) Polygenic Factors
D) Epigenetics – parent-of-origin and imprinting
2) Differences in the location of the genetic mutation

Question 11

what is a multfactorial mutation

Answer 11

Do not follow a simple Mendelian pattern
Environment factors increase or decrease risk
Occurs frequently in one gender more than the other
Occurs more frequently in specific ethnic group

Question 12

how is mutation reported

Answer 12

Type of mutations i.e. single gene deletion
Homozygous or Heterozygous
Position of the mutation:
1) Chromosome Number
2) Change in base-pair sequence
3) Which arm of the Chromosome
4) Position of the coding region
5) Protein it codes for
Affected Gene
Eg: Hemizygous missense (c.299T>G, p.(Leu100Arg))in the geneTYR

Question 13

what is dominant inheeritance

Answer 13

Dominant:
Only one parent is required to carry the mutated copy
Affected child often have an affected parent
Usually observed in every generation
Male to male transmission
50% chance if a parent is affected that their offspring will also be affected
New mutation can occur spontaneously – De Novo

Question 14

what is recessive inheritance

Answer 14

Recessive:
Two copies required from either parent
Parents may be unaffected but carry the gene
Not always seen in every generation – skip generations
More common in consanguineous families
Carriers (heterozygotes) are usually unaffected
Recurrence risk for offspring of two carriers is 25%

Question 15

what is x linked recessive inheritance

Answer 15

Males affected more than Females
Rarely Females are affected if both inherited alleles are mutated
Females are more often unaffected carriers
Affected males do not pass on their condition
Only mothers can be carriers to their son but not to daughters
Males have 50% chance of being affected if their mother is a carrier

Question 16

what is x linked dominant inheritance

Answer 16

Males and Females equally affected, although males more severely
No male to male transmission
Affected females can have affected sons and daughters
Offspring of an affected female have 50% chance of being affected

Question 17

how can inhertiance be mitchondrial

Answer 17

Affected Females are also carriers of the mutation
Offspring of an affected female, male or female, are affected
Affected Males are not carriers and do not pass the mutation on to their children

Question 18

what is cytogenetics

Answer 18

• Study of chromosomal mutations
• Cell are obtained from the DNA sample, grown and stained
• Chromosomes extract and placed on slides where they are observed by microscope
• Look at the number and structure of the chromosomes
• Fluorescence in-situ hybridsation (FISH) can be used to look at the chromosomes more closeley

Question 19

what is molecular genetics

Answer 19

-Study of single gene mutations
- Sequence of DNA code and observe for any changes
- too small to be observed under microscope so DNA has to be extracted and chemicals added to detect each base pair along the sequence
- this is then compared to the normal sequence and noted for mutations

Question 20

what is next generation sequencing

Answer 20

Targets a number of difference genes related to the phenotype
- Already a number of “Panels” available on the NHS
- May help to reduce the number of tests required for clinical diagnosis
- NHS UK Genetic Testing Network – https://ukgtn.nhs.uk/
- Eg: 15 Gene Exome (coding regions) Panel – 112 days and costs £850

Question 21

what is the 100,00 genome project

Answer 21

Government initiative started in 2012 to genome type (whole genome) 100,000 patients in the NHS with cancer or rare diseases from those with no previous genetic mutation
- Run by Genomic England and in collaboration with a number of specialist sites
- Geno-phenotype correlations
- Aim to detect new genes and biomarkers for treatment
https://www.genomicsengland.co.uk/initiatives/100000-genomes-project