Genetics and Inheritance 1 Flashcards
List the ways in which the genotype makes a major contribution to disease
Monogenic disorders
Polygenic disorders
genes can determine whether you can be resistant to a a disease
genotypes also controls the response to drugs
monogenic disorders
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
Polygenic disorders
Associated with more than one gene
Multifactorial - Environment, genetics - both of these determine the severity of the condition
eg. Ty
Genes determining whether you can be resistant to a disease
eg Individuals lacking CCR5 chemokine receptor which are immune to infection of HIV 1
Genotypes also controls the response to drugs
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
Describe how DNA is packaged to fit inside the nucleus
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
Describe the effects of the DNA structure on the transcription
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
Describe the human karyotype
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.
What are human chromosomes characterised boy
Size
Pattern
Location of the centrosome
- metacentric
- submetacentric - centromere nearer to the end
- acrocentric - centromere very close to one end
Name the two instances when chromosomes replicated
Mitosis
Meiosis
Describe Mitosis. Why is mitosis useful?
Leads to the production of 2 daughter cells of the same number of chronometer as the parent.
For development, growth, replacing lost/damaged cells
Describe Meiosis. Why is this necessary?
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
Compare and Contrast meiosis and mitosis
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)
How much of the Y chromosome confers maleness
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
Describe the part of the Y chromosome which confers maleness
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
Aneuploidy
When there is irregular number of chromosomes- one or more individual chromosomes present at an extra copy.
Trisomy 21 (Down syndrome) :
Cytogenetic nomenclature: 47, XX/XY +21
Regarded growth and development
Delayed mental and social skills
Complications:
Cardiac abnormalities
Increased incidence of acute leukaemia
Trisomy 13 (Patau Syndrome):
Cytogenetic nomenclature: 47, XX/XY +13
Common abnormalities:
Heart Defects
Incomplete brain development
Mean survival is roughly 130 days
Trisomy 18 (Edwards Syndrome)
Cytogenetic Nomenclature 47, XX/XY +18
Abnormalities:
Heart Defects
Intestines protruding outside the body
95% die in Utero
Why are trisomies persistent only in 13,18,21?
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
List the diseases with abnormal number of chromosomes
Kinefelter Syndrome
Turner Syndrome
XYY syndrome
Describe Klinefelter Syndrome
XXY
Can appear normal (health wise)
Diagnosis later on in life
Small testes ( limited development of secondary sexual characteristic)
Describe Turner Syndrome
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
XYY
Asymptomatic
47, XYY
Increased growth velocity , above average height
Why is it necessary to determine karyotype
Enables foetal diagnosis of chromosomes
What is amniocentesis?
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)
Why has the number of tests done by the NHS has rises?
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
What is Mendelian Inheritance relating to
Genotypes at a single locus- monogenic
What are Mendels Laws
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
Name the different types of Mendelian Inheritance
Autosomal Recessive Autosomal Dominant X linked Recessive X linked Dominant Mitochondrial
Autosomal Recessive
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
How can you tell the wild type version of CFTR is dominant?
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
Pedigree for Autosomal Recessive
The characteristic skips generation
Autosomal- so equally like thar male and female are affected
Trait is transmitted by either sex
Autosomal Dominant
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
How can you tell it is a Dominicans condition
Mutant polypeptide will aggregate regardless of presence of wild type protein
Autosomal Dominant Pedigree diagrams
Trait is frequent and present in each generation
The trait affects males and females equally
Trait is transmitted by either sex
X linked Recessive
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
Complex disorders
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
Describe the twin studies
Monozygotic
Dizygotic
Of the concordance of a trait is higher in MZ than DZ then the trait is primarily controlled by genetics
