Sex chromosomes Flashcards
Is the Y chromosome essential to life?
No, because females to do not possess it
Normally pairs of chromosomes recombine during meiosis and genetic information is swapped between them. What happens between the X and Y chromosomes and what does this mean?
- Normally pairs of chromosomes recombine during meiosis and genetic information is swapped between them. There is very little recombination between the X and Y chromosomes (roughly 3Mb out of the 60Mb length)
- The lack of recombination means that unlike all other chromosomes, the genetic information is passed unchanged from father to on except for mutations.
- Mutations can be insertion or deletion in the DNA, or a base change.
The bulk of the Y chromosome, which does not recombine, is called the “NRY”, or non-recombining region of the Y chromosome. Single-nucleotide polymorphisms (SNPs) in this region are used to trace direct paternal ancestral lines.
Why is the Y chromosome so useful to study?
- This combination of male specificity and the lack of recombination make the Y chromosomes useful to study.
- The Y chromosome has some quite unique properties.
What can the two ends of the Y chromosome do and what is generally studied?
- The two ends of the Y chromosome can recombine with the X chromosome, so when investigating Y chromosome only looking at the middle where recombination wont occur
What are the Y chromosome genetic uses?
- Relationship cases
- Anthropology/ geographic ancestry
- Criminal cases
The Y STRs has a slow discovery at first, when was the 1st Forensic Y-use workshop held and where?
Berlin in 1996
With the initial Y STR discovery, what were the 7 core loci recommended?
o DYS19
o DYS390
o DYS391
o DYS392
o DYS393
o DYS389 I and II
What was then suggested was added to the already existing 7 core STR loci when studying Y STRs?
- Suggested adding at least one of the loci DYS385, YCAII or YCAIII to the 7 core loci
- YCAII and YCAIII are Dinucleotide repeats and they have high stutter making analysis of profile complex, especially if have mixtures so focused on **DYS385 **as is a useful marker and therefore continued to be used
Today there are 13 core Y STR loci in use
in 1998, what was in use for studies for Y chromosome STRs?
- By 1998, still only 13 known polymorphic Y chromosome STRs.
- 4 have low genetic diversity.
To increase discrimination, it is possible to add what else?
Other Y STR loci
Tell me about the further discoveries for Y STRs?
- 12 new loci published in 2000
At the end of 2002, 14 new highly polymorphic Y STRs published. - Due to the fact that all the databases have been constructed using the markers that were first discovered, it is very hard to incorporate these newer STR loci.
Most laboratories performed Y STR testing using self-made reactions (this kit is PowerPlexY) until what was released in 2003?
Promega kit
What further Y STR amplification kits were developed and when?
- Applied biosystems (thermofisher scientific now) developed a kit which was released at the end of 2004 called Yfiler with a further 5 loci.
- Further advanced in Y-STR profiling kit not until 2012 (Y23 from Promega) and Yfiler Plus (2014)
Describe what this profile shows from the PowerPlexY kit
- Red size standard seen
- All have one marker as only 1 Y chromosome except with 385 which has two peaks as is polymorphic and is able to mutate separately
Tell me what is special about the 385 locus on the Y chromosome
Its a diallelic STR
o There are 2 copies of the 385 locus on the Y chromosome and so 2 products are produced. This is because a 190kb fragment of DNA has been inversely duplicated with 40kb separating the copies
o 385 loci is 190kb
In order to validate the PowerPlexY kit for forensic use, how is it validated?
- To validate the PowerPlex Y kit for forensic use, the performance of the kit has been assessed for a number of factors
- These include male specificity, sensitivity and mixture studies
What do these results show?
- A-D shows the levels of DNA
- Shows that even with 1000 fold more female DNA than male DNA, it was still able to pick out the male component
Why use haplotypes?
- Haplotype frequency databases
- Problems with reporting haplotype frequencies
- Mutations
In normal autosomal STR profiles (e.g., SGM+ profiles), each individual STR locus is independent. So, the allele at one STR can give no indication of what allele will be
For this reason, when the frequency of the profile is calculated, the individual allele frequencies can be multiplied together
How do you calculate the frequencies of haplotypes?
https://pbgworks.org/sites/pbgworks.org/files/measuresoflinkagedisequilibrium-111119214123-phpapp01_0.pdf
Haplotypes
* For example, in an autosomal profile the following alleles may be present
o TH01- 8, 9.3 (frequency is 2(0.1030.331)= 0.068)
o FGA- 21, 23 (frequency is 2(0.1770.154)=0.055) **
* To calculate the frequency of these alleles occurring in a particular individual, the frequencies for the different STRs can be multiplied together
* So, the frequency in the population of a TH01 (8, 9.3) and FGA (21, 23) being present in an individual is;
o 0.068*0.055= 0.0037
- In Y chromosome profiles, as the while chromosome in inherited unchanged, all the STRs are linked. As there is no independence between STRs, the frequencies cannot be multiplied together
- For example, there may be two rare alleles that occur in the same Y chromosome profile;
**o DYS19- 16 (frequency 0.056)
o DYS393- 12 (frequency 0.049) ** - If these frequencies were multiples together than that would suggest that the occurrence in the population of men with profiles containing 16 alleles at DYS19 and a 12 allele at **DYS393 was 0.0027 (0.27%) **
- However, since the STRs are linked it may be that even though both alleles are quite rare, they are often both present together in a particular individual, so the actual frequency of seeing these two alleles in a random male from the population is significantly higher than 0.27%
- All the STRs on the Y chromosome are linked.
- A Y chromosome profile is treated as a haplotype.
- So, the frequency of individual alleles is not important, but the frequency of the entire profile (haplotype) is.
- The frequency of the haplotype is therefore calculated by a simple counting method, how many times has this entire profile (haplotype) been seen before in the population.
- Therefore, to find the frequency of a haplotype, it is not necessary to have allele frequency data as for autosomal; STRs, but to have a haplotype frequency database.
- It is important to have haplotype data on the local populations.
What is the problem with using the haplotype frequency data?
- The drawback with just using this data is that the sample size is relatively small.
- This is why a global Y chromosome haplotype database has been established (1996).
Note:
* *may ask exam question on this idea and calculations
* Website for this database on ppt
What is the average mutation rate for Y chromosome STRs?
- The average mutation rate for Y chromosome STRs is often quoted as roughly 2.1x10-3 per locus per generation. That is to say that there are approximately **2-3 mutations for every 1000 Y chromosome STR loci **passed on.
- Recently more specific data on the 17 Yfiler STRs mutation rates varying between **2x10-4 to 6.5x10-3 **
Example of an extended family study
- The Scottish name Weir
o Derived from the Norman-French de Vere - Robert Weir or Vere
o Lived in Ireland hundreds of years ago
o Descended from the Royal Vere of Scotland
o 4 of the male samples tested were thought to be direct common descents of Robert Weir or Vere
o All described shared the same 11-locus haplotype
o Including rare duplications at three sites
** DYS389I 13, 14
DYS289II 29, 30
DYS439 11,13 **
Tell me about the inheritance of Chromsome X
- Males transmit** same **chromosome X to all their daughters
- All daughters and fathers share at least one allele at **every **X-linked locus
How do anthropologists use the Y chromosome?
- Anthropologists use the Y chromosome to examine population migration
- Using SNPs, which have a very low mutation rate, it is possible to study human origins and expansion out of Africa as well as more recent population sub-structuring
- The Y chromosome can be used to show divisions in the worldwide population according to ancestral lineage. These show similarities between neighbouring populations but variation between distant populations
What was constructed from anthropological studies and what did it suggest?
- Constructed a comprehensive haplogroup tree for most known polymorphisms on the non-recombining Y (NRY) chromosome in a single sample set
- All SNP profiles can be grouped into a haplogroup. As SNPs are generally ‘unique event polymorphisms’ the tree allows a full profile of 245 SNPs while only having to perform a minimum number of reactions
- Yellow dot is y chromosome Adam which is the idea that every individual alive today descends from a single common ancestor
Y chromosome and ancestry
Tell me about Rapidly mutating Y-STRs and why they can be useful
- First discussed in 2010 AJHG paper by Ballantyne et al.
o 186 Y STRs in 2000 father-son pairs
o 13 RM-Y STRs - 13 RM-Y STRs
- Preliminary study done in 2011
- Multicentre study started early 2012
- 12,272 samples from 111 worldwide populations
- Relative to Yfiler, haplotype diversity increased in 86% of populations
Rapidly mutating Y-STRs are like normal Y STRs but they mutate at a much higher rate than normal ones which can help with discrimination with a 10-100 fold higher mutation rate
- Why we want Y-STRs that mutate more rapidly? **to distinguish between father and son or brother to help discriminate between them **
- Not all RM-Y STRS are being used in kits as are hard to interpret but some are being used
