GH Revision - Part 1 (1-7) Flashcards
week 1- 4
What is a transcriptome?
all transcripts,
including alternatively spliced and structural RNAs
tissue specific!
What is a proteome?
all the proteins
What is the Exome?
The PROPORTION of genome that encodes for functional proteins/ exons
What are SNPs and what can we predict through identifying the prexene/ absence of them?
SNPs = difference or mutation in a single DNA base pair at a specific position in a population.
Some are very important in helping us predict disease risk, expressed traits and drug response.
How much of the total genome sequence does the protein coding region encompass?
1%
What are the 5 characteristics of a genome?
1- repetitive sequences (50%)
2- Pseudogenes (2000)
3- Simple sequence repeats
4- genes in introns of other genes
5- significant person-person structural variation
What makes up the ‘gene-dense’ parts of the human genome?
Urban centres= rich in G and C
How did the human genome project change science and medicine?
Spot potential disasters (cystic fibrosis, Huntington’s disease, cancer, arthritis, diabetes) LONG before it presents
expected to prove that high number of protein-coding genes = organism complexity BUT showed Non-Coding RNAs dramatically increase with developmental complexity
At what stage in Mitosis do human cells briefly contain twice the number of independent chromosomes?
Anaphase
Homologous chromosomes vs sister chromatids.
HC= same size, same genes in same location BUT DIFFERENT ALLELES (mum and dad)
SC= same size, same genes in same loci and SAME ALLELES
What is the process for viewing chromosomes?
a fetal cell sample taken (Ammniocentesis or chorionic villi sampling) –> centrifuge to collect cells –> growth of cells in culture medium,–> treat with Colchicine for hrs –> drop cells onto slide to spread chromosomes
Define metacentric, submetacentric and acrocentric.
Meta= divided equally
Sub= one long arm and one short
Acorcentric = located near one end
What was the scientific objectives of the human genome project?
sequence all DNA in the human genome , identify and map all of the genes within the genome
develop tools to obtain and analyse the date and make the information available to the public
What is Tay-Sachs disease and clinical symtoms?
What
- progressive neurodegenerative disoder in which brain cells are damaged and decline in CNS function
appear normal until 3-6months, then have:
-muscle weakness
-lose motor skills
-lose ability to reach and hold
-lose ability to smile
-progressive hearing and vision loss
-paralysis
Inheritance and cause of Tay-Sachs disease
Autsomal Recessive
mutation in HEXA gene (15q23)
HEXA gene encodes an enzyme beta-hexoaminidase A = affected = prevents breakdown of GM2 = accumulation of lipid in brain and spinal cord
What is the naming convention for chromosomes?
e.g Xp11.2
X= chromosome
P= arm
1= region
1= band
.2= sub-band
what are the five main causes of chromosome abnormalities and what do they result in?
Anaphase lag = monosomy
Chromosome missegregation = monosomy, trisomy and triploids and tetraploids.
meioric/mitotis failure = triploids and tetraploids
dispermy = triploids and tetraploids
incorrect DNA repair = deletions, duplications, Ring, translocations and inversions
triploidy vs trisomy
trisomy= extra copy of chromosomes
triploidy= three COMPLETE sets of chromosomes
What is anaphase lag?
one chromosomes fails to migrate to pole of spindle and is hence excluded from the daughter cell
monosomy
what is chromosome Missegregation ?
Non-disjunction
homologous chromsomes or sister chromatids fail to separte
Meiosis I vs Meiosis II erros with Non-Disjunction
I= three copies, non-idencial = all abnormal
II= three copies, two identical one not = 50% abnormal
what are the 4 ways in which meiotic and mitotic failure and dispermy arise?
1- complete non dis-junction
2- error in gamete formation (cytoplasm or cell as whole fail to divide)
3-error i early mitotic division (cytokinesis does not occur)
4- errors at fertilisation (dispermy, haploid egg + 2 haploid sperm)
What are the two types of inversions? chaacteristics
pericentric (includes centromere) and paracentric
don’t always result in abnormalities (if breakpoints do not disrupt genes)
what are translocation and what are their two types?
movement of genetic material to another nonhomologous chromosomes
insertional
reciprocal (exchange)
what are Robertsonian Translocations and what is the result?
centric fusions of acrocentric chromosomes → 2 acentric + 1 dicentric
- no net gain or loss of genetic material ∴ normal phenotype (balanced)
increased risk for fetal abnormalities or miscarriage
feature of deletions
size roughly correlates with severity of abnormality
How do ring chromosomes form?
when telomeres are lost, and sticky chromosome ends fuse
what karyotype disorders can Arise from non-disjunction?
trisomy 13, 18 and 21 or monsomy X (turners)
what are the genotypic and phenotypic ratios for F1 hybrid cross?
G= 1:2:1
P= 3:1
what is the phenotypic ratio for Di-hybrif cross?
9:3:3:1
what is conditional probability?
probability of one event, given that another event has already occured
(offspring’s genotype depends on parents)
Co-dominance vs incomplete dominance
Co= both alleles are fully expressed
incomplete= mix
epistasis
alleles in one gene masking the phenotypic effect of another
Bombay phenotype
hh individuals are blood type O, regardless of their alleles at the ABO locus
what is the formula for recombination distance?
no. of recombinants/ total progeny
what is the general format for mutations at DNA or RNA level?
prefix, position, reference base >new base
e.g g.AA>T
what is the general format for mutations at protein level?
prefix, amino acid affected, position number, new amino acid
Mendle’s Law of segregation
for any trait, the pair of genes of each parent will separate and nl==only one gene from each will pass on
Mendel’s law od independent assortment
two dif alleles will randomly assory= their alleles in gamete formation due to random arrangement of homologous chromosomes
what are the Automsomal recessive disorders?
Cystic fibrosis
PKU
Sickle Cell
Haemachromotosis
thalassemia
what are the features of autosomal recessive inheritance?
Horizontal - one or more affected siblings
parents and children normally unaffected
each subseuent sibiling of affected = 1/4 chance being affected
unaffected sibling of affected = 2/3 risk carrier
parents must be carriers
male and female equal
what is the carrier risk for cystic fibrosis?
1/25
compound heterozygotes
two different alleles, both of which are defective
What are the autosomal dominant diseases?
(growth)
Achondroplasia and hypochondroplasia
(neurological)
Huntington’s Disease
Myotonic dystrophy
(tumour supression)
retinoblastoma
neurofibromatosis
What are the features of Autosomal dominant?
vertical degree pattern
each child of affected parent has 1 in 2 chance of being affacted
males and females equallu affacted
unless stated otherwise, those marrying in = wild type
Expression and penetrance
Expression
-severity or mildness
Penetrance
-measure of chance
-some fully penetrant some only manifest if meet conditions
What is anticpation and what disorders does it impact?
increasing disease severity and or earlier age of onset in successive generations
repeat disorders (huntingtins and myotinc dystrophy)
X-linked recessive inheritance characteristics
Knight’s move pedigree pattern
parents and children normally health
NEVER transmitted FATHER –> SON
mostly males
female carriers
subsequent brothers of affacted boys = 50% chance
Sisters NOT affacted = 50% chance CARRIER
features of X-linked dominant
AFFECTED MALE passes to ALL daughters and NO sons
50% chance mother passes on
at least 1 parent with trait
more prevalent in females
Sex linked vs limited vs influenced
linked = controlled by genes on sex chromosomes
limited = only observed in one sex
influenced= alleles are dominant in one sex and recessive in the other
Mitochondrial inheritance inheritance patterns
vertical
female –> all kids
children of affected men NEVER affected
extremely vairble due to heteroplasmy and homosplasmy
Heteroplasmy and mitochondrial diseases
= cell or organism in which ALL copies of mitochondiral DNA are NOT the same
influences disease penetrance and expressivity
Five major points of pedigree analysis:
1- unaffected indv cannot have dominant disease
2- marrying in = assume wild type (not carriers)
3- unaffacted individual can be a carrier and must be indicated on pedigree
4- X-linked= single recessive can impact male
5- father transmits his allele of X-linked to daughter but not son, mother gives to both
