X-linked Flashcards
What is a X:A ratio?
The ratio of the number of X chromosomes to the number of autosomal sets
How do X:A ratios affect sex determination?
A diploid organism with two X chromosomes has an X:A ratio of 1:1 or just 1, meaning that they have one set sex determining x chromosomes (XX) and one autosomal set of chromosomes (AA), this is what females have. Individuals with one X chromosome, aka males (XY), have the ratio 1:2, or 0.50. This is due to their singular x chromosome (XY) and their pair of autosomal chromosomes(AA).
What would genotypes look like as X:A ratios?
- XY : AA = Male
- XX : AA = Female
What would the X:A ratio of a XY : AA be?
0.5 or 1:2 (because there is only one X chromosome and two A chromosomes)
What would the X:A ratio of a XX : AA be?
1 or 1:1 (because there are two X chromosomes and two A chromosomes)
What is the Sxl gene?
Sex-lethal (Sxl) is the master switch gene for somatic sex determination in Drosophila melanogaster.
How does the Sxl gene affect humans?
In XX animals, Sxl becomes activated and imposes female development; in X(Y) animals, Sxl remains inactive and male development ensues.
How do X:A ratios and the Sxl gene correlate?
If the X:A ratio is 0.5 (1:2) then the Sxl gene is turned off causing the embryo to become male. If the X:A ratio is 1 (1:1) then the Sxl gene is turned on and the embryo becomes female.
What happens to the X:A ratio and Sxl gene in cases of non-disjunction?
In cases of non-disjunction, where the number of chromosomes is abnormal, eg. XXY, the X:A ratio would depend on if there is more than one x chromosome. For example, for XXY the X:A ratio would be 1:1. This is due to there still being two x chromosomes and there is always at least two A chromosomes, hence the XXY would be female.
Draw a diagram of how X:A ratios and the Sxl gene works
https://docs.google.com/document/d/1Nzo4FTzXCbwOZjpoc_J_4IF3gsOXPcoyC2BowELmx0U/edit?usp=sharing
What happens to the Drosophila when there are more than two autosomal sets of chromosomes?
The influence on the number of autosomal chromosomes on sex is indirect, however, they could be affecting the timing of developmental events and therefore how long sex-determining genes on the X chromosome are active. For example, XX flies with three autosomal sets (XX, AAA) have an X : A ratio of 0.67 and develop an intersex phenotype. In these flies, the presence of three autosomal sets causes a critical developmental stage to shorten, not allowing female factors encoded on the X chromosomes enough time to accumulate, with the result that the flies end up with an intersex phenotype.
How does intersex occur in humans?
- SRY mutations, mixed chromosomal abnormalities or hormone deficiency/excess disorders, and various degrees of mosaicism of these and a variety of others.
- Intersex in humans: 47XXY, 46XX/46XY, or 46XX/47XXY or XX & XY with
What is mosaicism?
The property or state of being composed of cells of two genetically different types
Why do we need Gene Dosage Compensation of X-Linked Genes?
- X chromosome harbours 100s of genes necessary for normal development of both sexes
- The evolution of X/Y and X/O sex determination has necessitated the co-evolution of gene dosage compensation mechanisms for X-linked genes
How do x-linked genes differ for males and females
- Different mechanisms adjust for the unequal dosage of X-linked genes in male and female animals
What is an example of a Gene Dosage Compensation mechanism?
Hyperactivation of X-linked genes in males is when the SXL gene has been turned off, this then causes a protein complex to bind to the x chromosome and stimulate gene expression.
Why do males have to have mechanisms that increase the amount of x-linked genes that are expressed?
This is because females have two x chromosomes and therefore have more x-linked genes expressed. However, males only have one x chromosome and therefore need to have more of the genes on their only x-chromosome expressed so that they have the same or a similar amount as females. This is because the x-chromosome has many genes that make up a normal human.
What happens when there is too much or too little of SXL expression?
Inappropriate levels of SXL expression in either males or females will lead to lethality arising from inappropriate X chromosome dosage compensation.
Draw a diagram of Hyperactivation of X-linked genes
https://docs.google.com/document/d/1Nzo4FTzXCbwOZjpoc_J_4IF3gsOXPcoyC2BowELmx0U/edit?usp=sharing
What is the difference between gene dosage compensation in Drosophila and in mammals (humans specifically)
- Unlike the situation in Drosophila where the single male X chromosome is hyper-activated, in mammals one of the X chromosomes is inactivated.
- In this way the females don’t get a double dose of X related genes
What is the first step in the mechanism for X In-activation in female mammals?
- In every x chromosome there is a section called the x-inactivation centre (XIC) where a repressor of inactivation binds to one x chromosome.
What is the second step in the mechanism for X In-activation in female mammals?
- Inactivation spreads out from the XIC of the opposite x chromosome of which the repressors have not bound to
What is the third step in the mechanism for X In-activation in female mammals?
- The inactivation continues to spread until one of the chromosomes are completely inactivated.
Draw an label a diagram of the mechanism for x inactivation in female mammals
https://docs.google.com/document/d/1Nzo4FTzXCbwOZjpoc_J_4IF3gsOXPcoyC2BowELmx0U/edit?usp=sharing
When does x-inactivation occur?
- Inactivation events occurs when embryo consists of a few thousand cells
- Each cell makes an independent decision to inactivate one of its X chromosomes
How are the inactivated x chromosomes chosen and do they stay inactivated?
The chromosome to be inactivated is chosen at random and remains inactivated in all the descendent cells, except in female germ line cells where the inactivated X chromosome is reactivated
How are female mammals able to show two different phenotypes?
Female mammals are genetic mosacis
- A female, heterozygous for an X-linked gene, is able to show two different phenotypes
Do the inactive x chromosomes have any affect on the body?
The in-active X chromosome forms Barr bodies in the somatic cells of mammals
What is a Barr body?
- A small, densely staining structure in the cell nuclei of females, consisting of a condensed, inactive X chromosome
- It replicates out of step with other chromosomes in the cell
What is a well known example of x-inactivation?
In cats where a coat colour located on the X chromosome is dependant on the active x chromosome
- The X chromosome is randomly inactivated in somatic cells early in development
- Coat colour will depend on which X chromosome remains active
Draw a diagram of the inactivated x chromosome example for cats
https://docs.google.com/document/d/1Nzo4FTzXCbwOZjpoc_J_4IF3gsOXPcoyC2BowELmx0U/edit?usp=sharing
Since a female only needs 1 X chromosome can you survive if you are born with only 1 copy?
Turner syndrome (XO)
- 1:3000 female births
- underdeveloped secondary sex characteristics
- short, low hairline, broad chest
- folds of skin on neck, normal intelligence
What is Cytological Analysis
- Cytogenetic analysis usually focuses on chromosomes in dividing cells. It is the analysis of cells from the body under a microscope. This is done to determine what the cells look like, and how they form and function.
What is Karyotyping?
Karyotyping is the process of pairing and ordering all the chromosomes of an organism, thus providing a genome-wide snapshot of an individual’s chromosomes.
How is a Cytological Analysis carried out?
- Dyes such as quinacrine and Giemsa create banding patterns that are useful in identifying individual chromosomes within a cell
- A karyotype shows the duplicated chromosomes of a cell arranged for cytogenetic analysis
Draw and label a diagram on the process of a Cytological Analysis
https://docs.google.com/document/d/1Nzo4FTzXCbwOZjpoc_J_4IF3gsOXPcoyC2BowELmx0U/edit?usp=sharing
How are human chromosomes arranged into groups?
Human chromosomes are divided into 7 groups & sex chromosomes based on size & centromere location
What are the groups that human chromosomes are divided into?
- A 1-3: Large metacentric
- B 4,5: Large submetacentric
- C 6-12 & X: Medium sized, submetacentric
- D 13-15: Medium-sized acrocentric
- E 16-18: Short submetacentric
- F 19-20: Short metacentrics
- G 21,22 & Y: Short acrocentrics
Study the example of a Karyotype provided
https://docs.google.com/document/d/1Nzo4FTzXCbwOZjpoc_J_4IF3gsOXPcoyC2BowELmx0U/edit?usp=sharing
What is chromosome painting?
Chromosome painting is a term used to describe the direct visualisation using in situ hybridisation of specific chromosomes in metaphase spreads and in interphase nuclei.
What is a Euploid?
- Euploid organisms have complete sets of chromosomes (eg. Diploid = 2n)
What is a Polyploid?
- Polyploid organisms contain extra set of chromosomes (eg. Triploid = 3n; Tetraploid = 4n)
- Common in plants but rare in animals
What is a Aneuploid?
- Aneuploid organisms have particular chromosomes or parts of chromosomes under- or over-represented
- Aneuploidy—a numerical change in part of the genome
What is the difference between Aneuploidy and Polyploidy?
- Aneuploidy implies a genetic imbalance; polyploidy does not
What are “rearrangements” in genetics?
- Rearrangements are changes in chromosome structure.
What is Trisomy?
- Triplication of one chromosome
What is a Hypoploid?
- Hypoploid—an organism in which a chromosome or chromosome segment is underrepresented
What is a Hyperploid?
- Hyperploid—an organism in which a chromosome or chromosome segment is overrepresented
What is a Monosomy?
- Monosomy—the absence of one chromosome in an otherwise diploid individual
What is a common example of Trisomy?
- Down Syndrome, the 21st chromosome has a third copy
Other than Downs Syndrome, what other examples of Trisomy are there?
- Trisomies for chromosome 13 (Patau Syndrome) & 18 (Edward Syndrome) reported, but individuals usually die a few weeks after birth.
Why is it not recommended for older women to have children?
The frequency of nondisjunction increases with maternal age:
@ 25 years: 1 in 1500
@ 40 years: 1 in 100
What is the first step in the origin of Down Syndrome?
- In human females, meiosis begins in the fetus, but is arrested in prophase of meiosis I.
What is the second step in the origin of Down Syndrome?
- Prior to ovulation meiosis I is completed (and again arrested). The 2nd meiotic division only takes place after the oocyte is penetrated by the sperm.
What is the third step in the origin of Down Syndrome?
- In the first suspended state prior to ovulation, the chromosomes may become unpaired
- The longer the time in prophase, the greater the chance for unpairing and subsequent chromosome non disjunction
What causes Turner Syndrome to occur?
Turner syndrome (XO or 45, X) individuals can originate:
(a) from eggs or sperm that lack a sex chromosome
(b) from the loss of a sex chromosome in mitosis after fertilization —> Somatic Mosaics
What are one of the Affects of Turner Syndrome that has scientists baffled?
- 45, X individuals have no Barr bodies in their cells
- This means that they have the same number of active X chromosomes as normal XX females. So why aren’t they normal?
