Genetics 1 : Chromosomes, genetic counselling and ethics 1 Flashcards
What are chromosomes ?
Vessels of genetic inheritance and allow cellular DNa to be stabalised.
what happens in chromosomes during mitosis?
DNA replication
chromosome segregation
stable maintenance of genetic material through cell division
what happens in the chromosomes in meiosis?
two divisions – meiosis I and meiosis II
reduction of diploid to haploid
chromosome complement
what are key things that cause genetic variation in meiosis?
genetic recombination/synapsis:
faithful segregation
exchange of genetic material
describe the chromosome structure
short (p) arm, long (q) arm telomere: protect ends centromere: holds sister chromatids together chromosome segregation
define metacentric,
sub-metcentric and acrocentric
Metacentric - centromere placed in middle
Sub-metacentric - closer to one telomere
Acrocentric - centromere near telomere
what is the human karyotype?
2 haploid sets of 23 chromosomes
44 autosomes, 2 sex chromosomes
kayotyping: G-banded, classified according to size
what are the two type of chromosomal abnormalities?
Aneuploidy – too many or too few chromosomes
Structural – chromosome rearrangements
what are the two types of rearrangements?
Balanced rearrangements – translocations, inversions
Unbalanced rearrangements – deletions, duplications
what is the most common cause of aneuploidy?
non-disjunction during maternal meiosis I is the most common cause of aneuploidy
Describe what Trisomy 21 is and what the features are?
most common autosomal abnormality
- 1:700-1:1000 live births
maternal age effect: 1:35 at 43
learning difficulties, dysmorphic features, heart defects
what are the symptoms of Down’s ?
learning disabilities: mild to moderate
Dysmorphic features
Cardiac defects (40%)
Alzheimer’s 20-30 years earlier
Describe Trisomy 18 and some of the features?
severe mental disability
dysmorphic features: Micrognathia, prominent occiput
rocker-bottom feet, clenched fists with overlapping fingers
congenital heart defects
many die within weeks, 90% within 1 year
incidence: 1:3000
maternal age effect: 1:500 at age 43
primary trisomy 18: 47,XX,+18 or 47,XY,+18
Describe trisomy 13 and some of the features?
Severe mental disability
Dysmorphic features (cleft lip and palate, polydactyly, holoprosencephaly)
renal abnormalities, cardiac defects
many die within weeks, 95% within 1 year
incidence: 1:5000 live births ; maternal age effect: 1:1100 at 43
primary trisomy 13: 47, XY, +13 (or 47, XX, +13)
what is the biggest risk factor for trisomy?
main risk factor for trisomy is maternal age
what is the genetic abnormality in Klinefelter’s ?
XXY
what are the signs and sx of Klinefelter’s ?
tall stature, long limbs gynaecomastia (30-50%) small testes, sometimes Crypthochirdism infertility, azoospermia Delayed or incomplete puberty incidence: 1:500 to 1:1000 newborn males – often undiagnosed
what is the chromosomal abnormality in Turner Syndrome?
45,X monosomy 40-60%
what are the signs and sx of turner’s?
short stature
infertility
1 in every 2,000 live female births
maternal age is not a risk factor
what are the sx of XYY syndrome?
often asymptomatic
symptoms may include learning disabilities, speech delay, low muscle tone (hypotonia), and being taller than expected
usually normal sexual development, and normal fertility, sometimes develop testicular failure
what are the sx of triple X (XXX) syndrome?
largely asymptomatic
in 10% seizures or kidney abnormalities
may be taller but usually does not cause unusual physical features, nor infertility
increased risk of learning disabilities and delayed development of speech and language skills
incidence: 1:1000 newborn females
what is the mechanism of X-inactivation aka lysonization?
begins X inactivation centre (XIC)
X-inactive specific transcript RNA (Xist) expressed on inactive X
Xist transcripts coat X chromosome leading to inactivation
what is a robertsonian translocation?
fusion of two acrocentric chromosomes
most common: der(13;14), der(14;21)
phenotype normal in balanced carriers but reproductive risks
what is translocation Down’s?
translocation Down’s : fusion of long arms of chr 14 and chr 21
Describe reciprocal translocation
two-way exchange of material between any two non-homologous chromosomes
what is chromosomal inversion?
chromosome segment reversed and re-inserted
may be balanced or unbalanced
may involve centromere or arm
what is an isochromosome?
centromere fission
what is a ring chromosome?
telomeric region lost, arms fuse
what is duplication?
More than one copy of chrosome segment
what is deletion ?
chromosome segment is lost
can be large or small
what type of syndrome is cri du chat?
deletion syndrome
what are the signs and sx of cri du chat?
Cri-du-chat named for high-pitched cry incidence 1:20,000 to 50,000 newborns most de novo, 10% inherited slow growth, microcephaly moderate to severe mental disability
