Genetics and Inheritance 1

Question 1

List the ways in which the genotype makes a major contribution to disease

Answer 1

Monogenic disorders
Polygenic disorders
genes can determine whether you can be resistant to a a disease
genotypes also controls the response to drugs

Question 2

monogenic disorders

Answer 2

Associated with a single gene
Easy to track- ie. if you have the genotype you have the disease
Environment plays no role

eg. CF, Sickle Cell Anaemia

Question 3

Polygenic disorders

Answer 3

Associated with more than one gene
Multifactorial - Environment, genetics - both of these determine the severity of the condition

eg. Ty

Question 4

Genes determining whether you can be resistant to a disease

Answer 4

eg Individuals lacking CCR5 chemokine receptor which are immune to infection of HIV 1

Question 5

Genotypes also controls the response to drugs

Answer 5

Eg. Forms of cytochrome P450 responsible for the transformation of a CODEIN to MORPHINE (active)

bad in patients which are poor metabolisers- 2 copies of the allele CYP2D6. This results in the enzyme not being as efficient.

bad also when there is ultrarapidisation of metabolism of codein. Death can be caused to the depression in respiratory system.

Eg. The genotype can determine the drugs that are prescribed. Breast cancer- 10 types. With HER2, herceptin will block the activity of HER2 but herceptin is NOT effect against humans that don’t express HER2. The idea is to decrease the signalling and prevent cell division which ultimately decreases growth of the tumour

Question 6

Describe how DNA is packaged to fit inside the nucleus

Answer 6

1) Short region of DNA double helix
2) Complexed with histone proteins
3) Wrapped to form nucleosides- condensed
4) other proteins are associated- form chromosome

Question 7

Describe the effects of the DNA structure on the transcription

Answer 7

Information of the genes must be accessible
Eg. With the RNA polymerase

DNA can unwind to allow binding to contain transcription factor
- therefore it is expressed without disassembly

Question 8

Describe the human karyotype

Answer 8

46 chromosomes- 23 from each parents

22 pairs of autosome
1 pair of sex chromosome

Assessed by staining chromosomes from the metaphase stage

G banding is when the chromosomes are stained with GIEMSA
Gives alternating light and dark bands which helps identify each chromosome.

Question 9

What are human chromosomes characterised boy

Answer 9

Size
Pattern
Location of the centrosome
- metacentric
- submetacentric - centromere nearer to the end
- acrocentric - centromere very close to one end

Question 10

Name the two instances when chromosomes replicated

Answer 10

Mitosis

Meiosis

Question 11

Describe Mitosis. Why is mitosis useful?

Answer 11

Leads to the production of 2 daughter cells of the same number of chronometer as the parent.

For development, growth, replacing lost/damaged cells

Question 12

Describe Meiosis. Why is this necessary?

Answer 12

After 2 rounds of segregation, the number of chromosomes is halved (2n —> n )
This allows the number of chromosomes in offspring to return back to the normal number
Introduces variation between the offspring- recombination between homologous chromosomes

Question 13

Compare and Contrast meiosis and mitosis

Answer 13

Mitosis- One round of DNA replication and One round of chromosomal segregation
Meiosis - one round of DNA duplication and recombination and 2 rounds of chromosomal segregation.

Mitosis- 2 daughter cells. 46 chromosomes. Genetically identical in theory.
Meiosis- 4 ** daughter cells. 23 chromosomes. Genetically variable.

** 1 egg ( 3 Are lost)

Question 14

How much of the Y chromosome confers maleness

Answer 14

Two chromosomal abnormalities suggest that a small region at the end of the short arm of the Y is all that is needed to confer maleness.

XX with the Y region = male
XY without the Y region= female

Question 15

Describe the part of the Y chromosome which confers maleness

Answer 15

PAR- are found at both ends of the chromosome- does not differentiate the X to Y.

SRY- the gene that encodes a protein that acts as a testis determining factor. The only region that is required for a testis deterring factor. This is the ONLY region required for male development

Question 16

Aneuploidy

Answer 16

When there is irregular number of chromosomes- one or more individual chromosomes present at an extra copy.

Question 17

Trisomy 21 (Down syndrome) :

Answer 17

Cytogenetic nomenclature: 47, XX/XY +21

Regarded growth and development
Delayed mental and social skills

Complications:
Cardiac abnormalities
Increased incidence of acute leukaemia

Question 18

Trisomy 13 (Patau Syndrome):

Answer 18

Cytogenetic nomenclature: 47, XX/XY +13

Common abnormalities:
Heart Defects
Incomplete brain development

Mean survival is roughly 130 days

Question 19

Trisomy 18 (Edwards Syndrome)

Answer 19

Cytogenetic Nomenclature 47, XX/XY +18

Abnormalities:

Heart Defects
Intestines protruding outside the body
95% die in Utero

Question 20

Why are trisomies persistent only in 13,18,21?

Answer 20

Trisomies can be present in all chromosomes but only 13,18,21 persist because they are smaller.
This means Smaller number of duplicated genes- development can happen relatively normally

In contrast development cannot occur when trisomy on chromosome 10 development cannot cope due to the number of chromosomes involved

Question 21

List the diseases with abnormal number of chromosomes

Answer 21

Kinefelter Syndrome
Turner Syndrome
XYY syndrome

Question 22

Describe Klinefelter Syndrome

Answer 22

XXY

Can appear normal (health wise)
Diagnosis later on in life
Small testes ( limited development of secondary sexual characteristic)

Question 23

Describe Turner Syndrome

Answer 23

Monosomy
45, X

Diagnosis sometimes made late during adult life- usually due to investigation revealing short statute

No adolescent growth spurt

Ova degenerate in utero, limited development of secondary sexual characteristics

Question 24

XYY

Answer 24

Asymptomatic

47, XYY

Increased growth velocity , above average height

Question 25

Why is it necessary to determine karyotype

Answer 25

Enables foetal diagnosis of chromosomes

Question 26

What is amniocentesis?

Answer 26

Usually carried out during 15-20 weeks of pregnancy
Only offered when combined test in the 1st trimester indicates significant risk of miscarriage.

1) Involve injecting as needle into the amniotic sac
2) Foetal cells are isolated
3) Quantification of chromosomes 13,18,21
Counting the number of chromosomes

4) (grown in culture medium)
5) ( karyotype observed after 2 week)

Question 27

Why has the number of tests done by the NHS has rises?

Answer 27

Ageing population

As maternal gene increases, the incidence of trisomy increases

Sperm production is maintained throughout the lifetime of males
Oogenesis largely completed at birth, suspended in meiosis 10 resumes once a follicle releases its oocyte into Fallopian tube then arrests at meiosis II

KEY- Ova is old as the mother

Question 28

What is Mendelian Inheritance relating to

Answer 28

Genotypes at a single locus- monogenic

Question 29

What are Mendels Laws

Answer 29

Every Individual possesses a pair of alleles for given trait, one of which is passed onto offspring

Genes for different traits assort independently to each other

Question 30

Name the different types of Mendelian Inheritance

Answer 30

Autosomal Recessive
Autosomal Dominant 
X linked Recessive 
X linked Dominant 
Mitochondrial

Question 31

Autosomal Recessive

Answer 31

Eg Cystic Fibrosis- CFTR chromosome 7
Cystic fibrosis transmembrane conductance regulator (Chloride channels-pumps chloride out of the cell)

Normally CFTR pumps Cl- out of cells leads to water exiting the cell by osmosis, maintaining a mobile layer of mucus- takes away pathogens
Mutant CFTR would not leave the ER so no Cl- is pumped out. This means that the Cl- gradient is lost- mucus becomes thicker which leads to lung infection, blockage- BACTERIA ACCUMULATE

Question 32

How can you tell the wild type version of CFTR is dominant?

Answer 32

The phenotype of CFTR can mask the allele as one wild type copy is able to maintain the Cl- gradient

CFTR mutant is Recessive as it requires two copies of the same gene for the allele to be expressed

Question 33

Pedigree for Autosomal Recessive

Answer 33

The characteristic skips generation
Autosomal- so equally like thar male and female are affected

Trait is transmitted by either sex

Question 34

Autosomal Dominant

Answer 34

eg Huntington’s disease

Caused by mutations at the HD locus
Neurodegenerative disease; leading to gradual cognitive decline

Mutant HD haas more than 36 repeats ( normal=28) of the CAG
This leads to the aggregation of the protein (precipitates on the neural tissue), cytotoxicity, neuronal cell death.

This is all bad as the tissue can regenerate

Question 35

How can you tell it is a Dominicans condition

Answer 35

Mutant polypeptide will aggregate regardless of presence of wild type protein

Question 36

Autosomal Dominant Pedigree diagrams

Answer 36

Trait is frequent and present in each generation

The trait affects males and females equally

Trait is transmitted by either sex

Question 37

X linked Recessive

Answer 37

Genes that are present on the X chromosome exhibit unique patterns of inheritance in comparison with autosomal genes

Haemophilia A- mutation in gene for blood clotting factor VIII on X chromosome

Most frequently found in males
Cannot pass from father to son because Y is passed from father to son
All daughter of affected fathers are carriers

Question 38

Complex disorders

Answer 38

Most characteristics are controlled by genes at more than one locus- multi factoria

Splits into continuous and discontinuous (it either is or it isn’t )- Type II diabetes myelitis

Question 39

Describe the twin studies

Answer 39

Monozygotic
Dizygotic

Of the concordance of a trait is higher in MZ than DZ then the trait is primarily controlled by genetics