Genetics 3) Chromosomes 1 Flashcards
What is the function of chromosomes?
Allow cellular DNA to be stably maintained and function as vessels of genetic inheritance
How is 2.17m of DNA contained in 40um nucleus?
Structures such as nucleosomes and chromatin fibre
Describe the structure of chromosomes
Short arm and long arm
Telomeres to protect ends of chromosomes
Centromeres to hold sister chromatids together
What is the function of telomeres?
Protects ends of chromosomes so they aren’t recognised as DNA breaks do won’t be susceptible to DNA repair
What does metacentric mean?
Centromere is in middle of chromosome
What does sub-metacentric mean?
Centromere is closer to one telomere
What does acrocentric mean?
Centromere is very near telomere so short arm is very short
What is mitosis?
Type of cell division in which each parent cell gives rise to 2 daughter cells each having the same number of chromosomes as the parent
What are the 2 divisions in meiosis?
Meiosis I - reductional division
Meiosis II - equational division
Describe the human karyotype
Normal human somatic cell has 46 chromosomes
44 autosomes and 2 sex chromosomes
How is a person’s karyotype determined?
Using 20 metaphase cells stained with giemsa satin which reveals a unique banding that helps identify each chromosome
Describe the cytogenetic notation
Total number of chromosomes, sex chromosomes, irregularity
What are the types of chromosomal abnormalities
Aneuploidy
Structural
How can aneuploid gametes be generated?
Meiotic nondisjunction
During maternal meiosis I
During meiosis II if chromatids fail to separate leading to disomic gametes and nullisomic gametes
What happens if mitotic nondisjunction occurs early in the development of an initial trisomy conceptus?
1 copy of trisomy chromosome is lost
What is trisomy 21?
Down’s syndrome
What is the prevalence of trisomy 21?
1 in 700-1000 live births
What is the maternal age effect of trisomy 21?
1 in 35 at 43 years old
What are the clinical features of trisomy 21?
Learning defects Dysmorphic features Heart defects Early onset Alzheimers Intestinal blockage Short and broad hands
What is the karyotype for trisomy 21?
95% have primary (full) trisomy 47,XX,+21 or 47,XY,+21
1-2% have mosaicism 46,XX / 47,XX,+21
4% have translocation 46,XX,der(14;21)(q10;q10),+21
What is the incidence of trisomy 18?
1 in 3000
What is the maternal age effect of trisomy 18?
1 in 500 at 43 years old
What are the clinical features of trisomy 18?
Severe mental disability
Dysmorphic features - micrognathia, prominent occupant
Rocker-bottom feet, clenched fists with overlapping fingers
Congenital heart defects
What is the karyotype of trisomy 18?
Primary trisomy: 47,XX,+18 or 47,XY,+18
5% have mosaic form
What is the incidence of trisomy 13 (Patau’s syndrome)
1 in 5000 live births
What is the maternal age effect of trisomy 13?
1 in 1100
What is the maternal age effect?
Main risk factor for trisomy
Mitotic nondisjunction and recombination
What is the incidence of Kleinfelter syndrome?
1 in 500 to 1 in 1000 newborn males
What are the clinical features of Kleinfelter’s syndrome?
Tall stature, long limbs Gynaecomastic Small testes or cryptorchidism Infertility, azoospermia Delayed or incomplete puberty
What is the karyotype for Kleinfelter’s syndrome?
47,XXY
Mosaic: 47,XXY/46,XY
48,XXXY or 49,XXXXY
What is the incidence of Turner syndrome?
1 in every 2000 live female births
What are the clinical features of Turner’s syndrome?
Short stature
Infertility
Poor breast development
Constriction of aorta
What is the karyotype for Turner’s syndrome?
45,X monosomy
Mosaicism: 45X/46XX, 45,X/46XiXq, 45X/46XY
What is the incidence of XYY syndrome?
1 in 1000 newborn males
What are the clinical features of XYY syndrome?
Often asymptomatic Learning disability, speech delay Low muscle tone Taller than expected Normal sexual development and fertility but can sometimes develop testicular failure
What is the karyotype of XYY syndrome?
47,XYY
47,XYY/46,XY
What is the incidence of triple X syndrome?
1 in 1000 newborn females
What are the clinical features of triple X syndrome?
Largely asymptomatic
Seizures or kidney abnormalities in 10%
Taller
Risk of learning disabilities, delayed development of speech or language skills
Doesn’t cause unusual physical features or infertility
What is the karyotype of triple X syndrome?
47,XXX
47,XXX / 46,XX
What is the mechanism of X-inactivation?
Randomly occurs in all cells
2 weeks post fertilisation
Begins at X-inactivation centre
X-inactive specific transcript (List) RNA is expressed on inactive X
Xist transcripts coat X chromosome leading to inactivation
What is chromosome translocation rearrangement?
Chromosome segment is transferred to a non-homologous chromosome or to a new site on same chromosome
What is a reciprocal translocation?
2 way exchange of material between any 2 homologous chromosomes
Incidence of 1 in 500 newborn
Balanced carriers are phenotypically normal but carry reproductive risks
Chromosome segregation in carrier of autosomal translocation leads to 5 possible pairs of daughter gametocytes
What is a Robertsonian translocation?
Fusion of 2 acrocentric chromosomes
Incidence of 1 in 1000 newborns
Phenotype is normal in balanced carriers but has reproductive risk
What is the karyotype of translocation Down’s?
Carrier: 45,XX,-14,-21,+t(14q21q)
Affected: 46,XX,-14,+t(14q21q)
What is an isochromosome?
Centromere fission
2 identical arms - 1 duplicated and other is deleted
Give an example of a deletion syndrome
Cri du chat
What is Cri du chat syndrome?
Named for its high pitched cry
Incidence of 1 in 20,000-50,000 newborns
Most are de novo, 10% are inherited
Deletion on chromosome 5p
What are the clinical features of cri du chat syndrome?
Slow growth
Microcephaly
Moderate-severe mental disability
Give example of duplication and deletion of chromosome 17
Deletion - Smith magenis syndrome
Duplication - Potocki Lupski syndrome
