The pseudoautosomal regions or PARs are homologous sequences of nucleotides found within the sex chromosomes of species with an XY [1] or ZW [2] mechanism of sex determination.
The pseudoautosomal regions get their name because any genes within them (so far at least 29 have been found for humans) [3] are inherited just like any autosomal genes. In humans, these regions are referred to as PAR1 and PAR2. [4] 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 154 Mbp and 62 Mbp in total). PAR2 is at the tips of the long arms, spanning 320 kbp. [5] The monotremes, including the platypus and echidna, have a multiple sex chromosome system, and consequently have 8 pseudoautosomal regions. [6]
The locations of the PARs within GRCh38 are: [7]
Name | Chromosome | Basepair start | Basepair stop | Band [8] |
---|---|---|---|---|
PAR1 | X | 10,001 | 2,781,479 | Xp22 |
Y | 10,001 | 2,781,479 | Yp11 | |
PAR2 | X | 155,701,383 | 156,030,895 | Xq28 |
Y | 56,887,903 | 57,217,415 | Yq12 |
The locations of the PARs within GRCh37 are:
Name | Chromosome | Basepair start | Basepair stop |
---|---|---|---|
PAR1 | X | 60,001 | 2,699,520 |
Y | 10,001 | 2,649,520 | |
PAR2 | X | 154,931,044 | 155,260,560 |
Y | 59,034,050 | 59,363,566 |
Normal male therian 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. [9]
Pseudoautosomal genes are found in two different locations: PAR1 and PAR2. These are believed to have evolved independently. [11]
in mice, some PAR1 genes have transferred to autosomes. [13]
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. [16] 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, [17] 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 [18] and Madelung's deformity.
Meiosis (; from Ancient Greek μείωσις 'lessening', is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one copy of each chromosome. Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a zygote, a cell with two copies of each chromosome again.
A sex-determination system is a biological system that determines the development of sexual characteristics in an organism. Most organisms that create their offspring using sexual reproduction have two common sexes and a few less common intersex variations.
Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.
Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.
The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the Y chromosome causes offspring produced in sexual reproduction to be of male sex. In mammals, the Y chromosome contains the SRY gene, which triggers development of male gonads. The Y chromosome is passed only from male parents to male offspring.
An inversion is a chromosome rearrangement in which a segment of a chromosome becomes inverted within its original position. An inversion occurs when a chromosome undergoes a two breaks within the chromosomal arm, and the segment between the two breaks inserts itself in the opposite direction in the same chromosome arm. The breakpoints of inversions often happen in regions of repetitive nucleotides, and the regions may be reused in other inversions. Chromosomal segments in inversions can be as small as 1 kilobases or as large as 100 megabases. The number of genes captured by an inversion can range from a handful of genes to hundreds of genes. Inversions can happen either through ectopic recombination between repetitive sequences, or through chromosomal breakage followed by non-homologous end joining.
X-inactivation is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome.
Y linkage, also known as holandric inheritance, describes traits that are produced by genes located on the Y chromosome. It is a form of sex linkage.
Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts another.
The pachytene stage, also known as pachynema, is the third stage of prophase I during meiosis, the specialized cell division that reduces chromosome number by half to produce haploid gametes. It follows the zygotene stage and is followed by the stage Diplotene
The short-stature homeobox gene (SHOX), also known as short-stature-homeobox-containing gene, is a gene located on both the X and Y chromosomes, which is associated with short stature in humans if mutated or present in only one copy (haploinsufficiency).
Léri–Weill dyschondrosteosis or LWD is a rare pseudoautosomal dominant genetic disorder which results in dwarfism with short forearms and legs and a bayonet-like deformity of the forearms.
Sex chromosomes are chromosomes that carry the genes that determine the sex of an individual. The human sex chromosomes are a typical pair of mammal allosomes. They differ from autosomes in form, size, and behavior. Whereas autosomes occur in homologous pairs whose members have the same form in a diploid cell, members of an allosome pair may differ from one another.
Interleukin 9 receptor (IL9R) also known as CD129 is a type I cytokine receptor. IL9R also denotes its human gene.
Synaptonemal complex protein 3 is a protein that in humans is encoded by the SYCP3 gene. It is a component of the synaptonemal complex formed between homologous chromosomes during the prophase of meiosis.
Protein sprouty homolog 3 is a protein that in humans is encoded by the SPRY3 gene.
Prader-Willi/Angelman region-1, also known as PWAR1, is an exon of the lncRNA Small nucleolar RNA host gene 14 (SNHG14).
Serine/threonine-protein kinase PRKY is an enzyme that in humans is encoded by the PRKY gene.
Non-allelic homologous recombination (NAHR) is a form of homologous recombination that occurs between two lengths of DNA that have high sequence similarity, but are not alleles.
Short-stature homeobox 2, also known as homeobox protein Og12X or paired-related homeobox protein SHOT, is a protein that in humans is encoded by the SHOX2 gene.