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The pseudoautosomal regions, PAR1, PAR2, and PAR3, are homologous sequences of nucleotides on the X and Y chromosomes. Although genetic recombination (occurring during sexual reproduction) is known to be limited only to the pseudoautosomal regions (PAR1 and PAR2) of the X and Y chromosomes, a 2013 study reports allelic unequal recombination between the X-chromosome-transposed region (XTR) Yp11.2 and Xq21.3, indicating the presence of a new PAR, which has been named PAR3. This PAR3 region is exhibited in 2% of the general population. Also, the additional layer of justification has been provided from another study on six dyslexic cases which were shown to harbor duplications and deletions in the same Xq21.3 and Yp11.2 regions through allelic unequal recombination.
Contents
The pseudoautosomal regions get their name because any genes within them (so far at least 29 have been found) are inherited just like any autosomal genes. PAR1 comprises 2.6 Mbp of the short-arm tips of both X and Y chromosomes in humans and great apes (X and Y are 155 Mbp and 59 Mbp in total). PAR2 is at the tips of the long arms, spanning 320 kbp.
Location
The locations of the PARs within GRCh38 are:
PAR1: chrY:10,000-2,781,479 and chrX:10,000-2,781,479
PAR2: chrY:56,887,902-57,217,415 and chrX:155,701,382-156,030,895
PAR3: chrY:3,571,959-5,881,959 and chrX:89,145,000-92,745,001
Inheritance and function
Normal male mammals have two copies of these genes: one in the pseudoautosomal region of their Y chromosome, the other in the corresponding portion of their X chromosome. Normal females also possess two copies of pseudoautosomal genes, as each of their two X chromosomes contains a pseudoautosomal region. Crossing over between the X and Y chromosomes is normally restricted to the pseudoautosomal regions; thus, pseudoautosomal genes exhibit an autosomal, rather than sex-linked, pattern of inheritance. So, females can inherit an allele originally present on the Y chromosome of their father.
The function of these pseudoautosomal regions is that they allow the X and Y chromosomes to pair and properly segregate during meiosis in males.
Genes
Pseudoautosomal genes are found in two different locations: PAR1 and PAR2. These are believed to have evolved independently.
PAR1
in mice, some PAR1 genes have transferred to autosomes.
PAR2
PAR3
~5–6 Mya, the Xq21.3 region has a history of duplication and transposition activity by means of a duplicated and later transposed block of 3.5 Mb from the X to the Y chromosome. This process is very similar to the origination of the PAR2. The PARs have a large amount of homology to each other, whereas the XTR alone has 98.78% identity. The genes PCDH11X and TGIF2LX have 99.1% identity with their PCDH11Y and TGIF2LY homologues in the XTR. A few genes in PAR1 and PAR2 are known to escape inactivation in the inactivated chromosome. Likewise, a few genes in Xq21.3 escape inactivation. Exon duplication and shuffling, as well as gene fusion, represent common features of the origination of the PARs. Similarly, gene duplication and recombination has been found between the Xq21.3 and the Yp11.2 regions in the present study. PAR2 and PAR3 share a similar type of origin and creation. PAR2 is found to exhibit a much lower frequency of pairing and recombination than PAR1. Thus, one can expect varied frequency of recombination in each of these PAR regions. Since PAR3 is located 700 kb away from the pseudoautosomal boundary (PB) 1 of PAR1 and Yp regions, the PAR3 might also be the extensions of PB of PAR1, but the flanking sequences suggest otherwise as the sequences do not show any homology with the PAR1 of X chromosome. Since Xq21.3 and XTR of Yp11.2 PAR3 share >98 % sequence homology, it is more likely that the recombination is possible between the PAR3 regions. In support of this, authors have found 2% of the control population showing the presence of Yp11.2 chromosomal segment in the X chromosomes of the normal female. Thus, these recombination events confirm XTR as a PAR3 region. These shared features between the PARs and the XTR suggest that the XTR of the human sex chromosomes is a new PAR, namely, PAR3.
Pathology
Pairing (synapsis) of the X and Y chromosomes and crossing over (recombination) between their pseudoautosomal regions appear to be necessary for the normal progression of male meiosis. Thus, those cells in which X-Y recombination does not occur will fail to complete meiosis. Structural and/or genetic dissimilarity (due to hybridization or mutation) between the pseudoautosomal regions of the X and Y chromosomes can disrupt pairing and recombination, and consequently cause male infertility.
The SHOX gene in the PAR1 region is the gene most commonly associated with and well understood with regards to disorders in humans, but all pseudoautosomal genes escape X-inactivation and are therefore candidates for having gene dosage effects in sex chromosome aneuploidy conditions (45,X, 47,XXX, 47,XXY, 47,XYY, etc.).
Deletions have also been associated with Léri-Weill dyschondrosteosis and Madelung's deformity.