Flashcards in cytogentic basis of inheritance Deck (93):
study of chromosomes within a cell.
what is conventional cytogenetic analysis
metaphase chromosome analysis (chromosomes are condensed and can be visible)
what is molecular cytogenetics
cytogenetics analysis at the molecular resolution at all stages of the cell cycle- DNA in situ.
examples of molecular cytogenetics
• Microarray CGH
• Next generation sequencing (NGS)
How long does the cell cycle take
what are the different stages in the cell cycle
growth phase 1
growth phase 2
how long is growth phase 1 of the cell cycle and what happens during this phase
cellular components are duplicated excluding chromosomes.
how long is the synthesis phase of the cell cycle and what happens during this phase
each of the 46 chromosomes is duplicated by the cells.
how long is growth phase 2 of the cell cycle and what happens during this phase
the cell double checks the duplicated chromosomes for errors and make needed repairs.
how long is mitosis
What are the stages of mitosis
Interphase, prophase, metaphase, anaphase, telophase and cyokinetics.
what happens in each stage of mitosis
• Interphase- all chromosomes loose
• Prophase- chromosome condense
• Metaphase- chromosome (made of 2 chromatids)- line up along the midline.
• Anaphase- the sister chromatids are separated
• Telophase- the cell begins to split into 2
• Cytokinesis- cell splits in 2 cells and chromosomes unwrap again.
In what stage of the cell cycle does G banding take place
How are chromosomes laid out on the template slide for G-banding.
line up chromosomes 1- 23, paired up and in order.
what are the main 2 types of cytogenetic abnormalities.
what is the dosage effect
(type of cytogenetic abnormality)
gain or loss in chromosome number
(loss is worse)
How can a gene be disrupted
breakpoint, inappropriate activation/ inactivation.
define genomic imprinting
alleles from 1 parent are suspended.
what is the position effect on a gene
A gene in a new chromosomal environment functions inappropriately
what has a more severe phenotype sex chromosome imbalance or autosomal imbalance.
gain (trisomy) or loss (monosomy) of chromosomes
gain whole sets (triploidy or tetraploidy)
diploidy and anueploidy is one human genome.
where do numerical abnormalities arise ( in which stage of cell development)
gametogenesis (meiosis- most errors in female meiosis)
early cleavage (post zygotic non disjunction).
what factors increase the risk of numerical abnormalities in chromosomes during gametogenesis.
maternal age >35
what are the stages in meiosis.
prophase 1- DNA replicate
Metaphase 1- chiasmta visible
Anaphase 1- chromosome separation
Telophase- cells begin to separate
Cytokinesis- secondary gametocyte.
Meiosis 2 - sister chromatics are pulled apart.
what is the most common meiotic error
when does chromosome disjunction occur in meiosis and what does it form
2 disomic gametes ( which have twice the content of normal gametes)
2 nullisomic gametes ( no content)
when does chromatid disjunction occur in meiosis and what does it form
1 disomic 1 nullisomic and 2 normal gametes.
most common 3 autosomal anueplodiues
Trisomy 21, trisomy 18 and trisomy 13.
what are the head abnormalities seen in a patient with trisomy 21
Eyes: upward slanting; brushfield spots (on iris)
Ears: abnormally shaped/low set
General – flat face, brachycephalic, short neck .
what percentage of children with trisomy 21 spontaneously abort
what are the neurological abnormalities seen in a patient with trisomy 21.
Learning disabilities (mild to moderate IQ 30-60)
what are the hands and feet abnormalities seen in a patient with trisomy 21.
single palmar crease
short broad hands
5 th finger clinodactyly- small finger.
wide sandal gap.
what fertility problems do males and females with trisomy 21 face
what other conditions are individuals with trisomy 21 more prevalent to.
obesity/ coeliac, arthritis, diabetes, hearing loss seizures.
what percentage of trimsomy 18 spontaneously abort
what head abnormalities seen in a patient with trisomy 18.
microcephaly, low set ears, micrognathia (small jaw), cleft lip and palate
what are the hands and feet abnormalities seen in a patient with trisomy 18.
clenched hands (seen on scan)
overlapping fingers (rocker bottom feet).
what mental abnormalities seen in a patient with trisomy 18.
what organ malformation occurs in trisomy 18
umbilical and inguinal hernia
congenital heart disease
congenital kidney abnormality
eye abnormality (cataracts and micropthalmia)
what percentage of trisomy 13 spontaneously abort
what are mental abnormalities seen in a patient with trisomy 13.
Mental retardation severe
Microcephaly/ sloping forehead
Defects of brain – holoprosencephaly
What are the hand and feet abnormalities of trisomy 13
Polydactyly & fingers flexed
what are the head abnormalities of trisomy 13
Eyes – microphthalmia, coloboma, retinal dysplasia, palpebral fissures slanted
Cleft lip and/or palate
Ears abnormal and low
Can have Cyclops
what other abnormalities of trisomy 13 are evident
what types of structures of the human body does trisomy 13 present with
midline structures are affected
How long do female eggs stay in meiosis 1
foetus 5 months until puberty
when do eggs go into meiosis 2
once they have been fertilised or bleed out in puberty.
what is age dependent deterioration of meiotic structures
long the eggs stay in meiosis 1 more likely the environment will impact them) - hormonal imbalance, irradiation, oral contraceptives, alcohol
Are sex chromosome anueploidies age dependent
Are autosomal anuplodies age dependent
Yes- maternal age.
give 2 examples of conditions which are sex chromosome anueplodiy
Turners (45 X)
What reproductive problems are faced with turners syndrome
Loss of ovarian function
what lymphatic problems do people with turners syndrome face
Swelling of hands &/or feet
what other abnormalities do people with turners have
Skeletal Abnormalities – short stature
Coarctation of aorta
IQ generally normal/reduced compared to sibs
how is klinefelters diagnosed
infertility or hypogonadism.
what fertility problems do patients with klinfelters face.
lack secondary sexual characteristics
Testicular dysgenesis (abnormal development.
what growth problems do people with linfelters face
Normal in infants, then accelerates
Adults long legs and arms
What are the 2 main errors in fertilisation
1.Polyploidy (usually triploidy)
2.Molar pregnancy (double paternal, no maternal)- no genetic content.
what percentage of triploides spontaneously abort
twice the genetic content in egg
twice the genetic content in the sperm.
2 sperm fertilise 1 egg
what is the consequence of double maternal content
Macrocephaly - all available nutrients fo to the brain to ensure survival.
significant grwoth delay.
what is the consequence of double paternal content
some growth delay
what does the maternal genome code for foetus or placenta
what does the paternal genome code for foetus or placenta
consequences of a molar pregnancy
Double paternal genome
Massive cystic placenta
define molar pregnancy
haploid sperm and empty egg results in haploid zygote
when does monocaism happen
2 main types of chromosome rearrangements
2 types of translocations
2 types of inversions
what is reciprocal translocation
• Break and exchange
• Content is the same just rearranged
each type you break a chromosome what is the % chance that you will break a gene
what is a robertsonian translocation
whole arm fusion
what chromosome undergo robertsonian translocation
does the long q arm of short p arm contain DNA information
long q arm.
is there reproductive risk in robertsonin and reciprocal translocation
define pericentric inversion
breaks either side of centromeres
what is paracentric inversion
breaks on one side of the chromosome.
do inversion have a reproductive risk
In robertsonian tranlocations is the phenotype of the patient affected
No, all genetic material is still present
q ars fuse and p are lost (but p has no genetic information)
unbalanced rearrgaments can be caused by
CNV- copy number variation
Deletions and duplications
2 types of deletions
what is a interstitial deletion
segment lost from within the chromosome.
what is a terminal deletion
segment lost from the end of the chromosome.
what is worse a chromosome loss of duplication
what causes the phenotype in deletions and duplications
abnormal gene dosage.
what causes deletions and duplications to occur
• Mediated by low copy repeats or duplications.
• Defined regions of repetitive DNA
• So when chromosome line up the similar regions can mismatch and pair together.
• Chaismata occurs leading to deletion and duplication.
what causes variable clinical expression of deletions and duplications
variable size of imbalance, other genetic and environmental effects