Flashcards in Sex Linkage And Chromosome Rearrangements Deck (43):
Which aneuploid sex chromosome combinations are viable in drosophila and humans?
Drosophila- XXY (female) XO (male)
Humans- XO XXX (female), XXY (male)
What are the long and short arms of a chromosome called?
What are metacentric, acrocentric and telocentric chromosomes?
Metacentric- centromere at centre
Acrocentric- closer to one end
Telocentric- near the very end
Where does proof of the chromosome theory come from?
Thomas Hunt Morgan made reciprocal crosses in Drosophila
-> Gave different result depending on whether Male/female carried the mutant allele
(X^W is recessive for white eyes)
X^WY mutant Male
X^WX^W mutant female
-> Pattern of inheritance follows that of X chromosome (physical object)
What was definite proof of the chromosome theory?
-> females that produce only X^WX^W eggs or O eggs
-> Cross with XY
Define sex linkage and give examples
Genes carried on X chromosome. When recessive:
- Transmitted mainly through females
- Manifests mainly in males
• Colour blindness
• Lesch-Nyhan syndrome- fatal error in purine metabolism
• Haemophilia/factor VII deficiency
Outline Lesch-Nyhan syndrome
• Mutation in HPRT gene on X chromosome- sex linked
• HGPRT deficiency causes Utica acid build up in body fluids
• Fatal error in purine metabolism
• Leads to self mutilation and death
• Affects 1/380,000 live births
Outline haemophilia A
• X-linked recessive
• Deficiency in factor VIII, causes increased bleeding as blood can’t clot properly
• Mild haemophilia A can occur in heterozygote females due to XCI
• 1/5000 males
Define lyonisation and give examples
X-chromosome inactivation. Females randomly inactivate one X in each cell early in development- Barr body in cell nucleus
• Tortoiseshell cat- patches of orange and black fur
• Colour blindness in human females- patches of normal and colour blind cells in retina
• Duchenne muscular dystrophy- heterozygous female twins, one with, one without.
What determines sex in humans, insects and birds and butterflies?
Insects- number of Xs
Humans- presence of Y
Birds and butterflies- males are homogametic WW and females are heterogametic ZW
What is cytogenetics?
The study of chromosomes
Why do we study whole chromosomes?
1. Many human diseases are associated with whole chromosome changes
• Cancers often associated with chromosome arrangements
• Patau syndrome- Trisomy 13
2. Evolutionary genetics
• Chromosome 2 in humans is result of fusion of two primate chromosomes
Section where the chromosome attaches to the spindle during cell division
Repeated sequence at the end of each chromosome.
Protect ends of chromosomes- prevent from binding to others.
Define deletion and give an example
Section of chromosome is removed (deletion loop is formed)
• Notch wing in Drosophila- dominant X chromosome mutation. Homozygotes lethal
• Cri-du-chat in humans- tip of chromosome 5 is lost- causes pinched facial features, mental retardation, cat-like cry
Define duplication and give examples
Common. A section of chromosome is doubled up. Important force in evolution.
Tandem ABCBCD, reverse ABCCBD
• Globin gene families- alpha and beta groups on different chromosomes
• Odorant gene family
What is replication slippage? Give an example
• tandem duplication
• chiasma forms
• results in further duplication
Important force in mutation
Drosophila bar eye:
• Results from tandem duplication
• Cross two bar eye flies together and can result in normal and double bar eyed flies
• Due to chiasma forming and crossing over
• increase in number of CAG repeats
Rare. Section of chromosome rotated and reinserted. Often viable as no change in amount of material.
Prevents crossing over of inverted chromosomes with unconverted chromosomes as a dicentric and acentric (centromeres) fragment are formed
Acentric lost at cell division
In heterozygotes for the inversion, abnormal gametes will be formed. Excess of some genes, deficient of others. Small-> viable gametes, abnormal child, large-> lethal
Give an example of inversion
Some drosophila species have many overlapping inversions all over their chromosomes- all multiple inversion heterozygotes.
-> No recombination at all. One fixed set of genes
Define translocation and give an example
Two non-homologous chromosomes exchange parts
• Associated with cancers- chronic myeloid leukaemia- 9-22 translocation, Burkitt’s lymphoma- 8-14 translocation
Outline Burkitt’s lymphoma
• Disease of lymphatic system
• extended lymph glands in the neck
• Translocation from c8 to c14
• Translocation of oncogene next to an active immune system gene- position effect variegation
• Lymphoma gene is more active than it should be
What has translocation been used for?
1. Releasing insects with translocations means it will become more and more common-> most of offspring will be heterozygous and will die
• Was used to wipe out tsetse flies in parts of Africa, responsible for transmitting sleeping sickness.
2. Used in mapping genes such as Testis-determining Factor (TDF/SDY). XX males have crucial part of Y translocated onto X so search narrowed down.
3. Suggested position effect variegation
Define position effect variegation and give an example
A gene’s effect can be modified by it’s position on a chromosome
Red eye/white eye Drosophila
Translocation of recessive allele to somewhere else= mixture of red and white eye phenotype
Translocation of oncogenes to somewhere on the genome near a more active promoter- spreads faster
• Burkitt’s lymphoma
What is a Giemsa stain?
G-banding- staining of condensed chromosomes to produce a visible karyotype
Outline how cancer can involve chromosomal changes
1. Deletions- loss of tumour suppressor genes
2. Duplications- doubling up of Porto-oncogenes- promote cell division
3. Translocations- activity of genes can be increased if they’re moved next to different genes. Eg, Burkitt’s lymphoma- proto-oncogene in chromosome 8 moved close to a gene that controls expression of antibodies in B-lymphocytes on c14-> increase expression
What is nondisjunction?
Error in cell division resulting in trisomy and monosomy
Outline Down’s syndrome
• Trisomy 21 causes 95%
• 88% maternal gamete nondisjunction, 8% paternal
• Can be caused by mosaicism- mitotic nondisjunction after conception
• Translocation of part of c21 onto c14- Down’s with only 46 c’s
• 1/800 births- increase with mothers age
• Low IQ(20-50), happy disposition, flattened face, short hands and feet, breathing difficulties, single palmar crease
Outline Turner’s syndrome
• Sterile- suggests 2X needed for normal development despite lyonisation
• High risk for heart disease
• Majority of cases spontaneously abort- rather than Klinefelters
What are XYY and XXX?
• effects on impulse control
• no symptoms- X inactivated by lyonisation
• May lead to sterility and sometimes low IQ
• Up to 8 Xs have been found
Outline Edwards syndrome
• Organ abnormalities
• Die within a few weeks of birth
Trisomies of larger chromosomes never seen, die early in development. In spontaneous abortions incidence of trisomy is high 1/2.
What causes gynandromorphs? Give an example
XX nondisjunction in early development
Eg, Drosophila heterozygous for sex-linked recessive white eye: Some have one red eye (XX female) one white (XO male)
What is haplodiploidy sex determination?
Ants, bees, wasps
Males are haploid n
Females are diploid 2n
Outline Klinefelter syndrome
• Some female characteristics
• Low steroid levels
• Up to 6X and 1Y found- still male
What is polyploidisation?
Changes in number of chromosome sets
Odd numbers > infertility
What is autopolyploidy?
Multiplication of the number of sets of chromosomes within a particular species
What is allopolyploidy?
Hybridisation of species and mixing of their chromosome sets
What ploidy is today’s wheat?
Why are bananas sterile?
They’re triploid so have an odd number of chromosomes
What is triticale?
A recent allopolyploidy of emmer wheat and rye.
Grows in dry cold conditions, used as animal feed
How are seedless fruits made?
Adding colchicine to cells in culture medium increases frequency of polyploidisation
Triploids formed and are sterile
Describe polyploidy in humans
Occasionally babies born with mix of polyploid and diploid cells- chimaeras, but die very young
Give an example of polyploidy in cancer
Adenocarcinoma- nearly all cells have 4n
• Generate large and competitive cells which can simultaneously evolve resistance to several anti cancer drugs as they have extra copies of their genome
• Can see particularly in methotrexate resistance
• May be multiple copies of resistant chromosomes- why cancers return after “cure”