Z3289829: Created page with "'''Reason for low contribution in Group 3 project: Klinefelter's Syndrome''' The reason may be due to me uploading my work in chunks. Below is my contributions to two sections ..."

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Created page with "'''Reason for low contribution in Group 3 project: Klinefelter's Syndrome''' The reason may be due to me uploading my work in chunks. Below is my contributions to two sections ..."

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'''Reason for low contribution in Group 3 project: Klinefelter's Syndrome'''

The reason may be due to me uploading my work in chunks. Below is my contributions to two sections in the project;

==History==

[[File:Steps in a classic array CGH-analysis used for the most common chromosomal abnormalities.png|thumb|right|250px|Figure 2:Steps in a classic array CGH-analysis used for the most common chromosomal abnormalities]]

Klinefelter syndrome (KS) was first described by Harry F. Klinefelter and his colleagues in 1942. Their observations of nine patients where characterised by a number of peculiar symptoms; [[#Glossary | '''gynecomastia''']], [[#Glossary |'''azoospermia''']], hyalinised and small testes, absent [[#Glossary|'''spermatogenesis''']], elevated levels of follicle-stimulating hormone (FSH) and [[#Glossary| '''hypogonadism''']]. <ref name="PMID17415352"><pubmed>17415352</pubmed></ref> <ref name="PMID21397196"/>
In 1956, an investigation was carried out with 7 patients with Klinefelter’s syndrome that had the buccal smears that demonstrated Barr bodies . However, the cause of the syndrome remained unknown until 1959, when Jacobs and Strong discovered that a patient with KS had 47 chromosomes, including an extra X chromosome in the karotype of the patient <ref name="PMID17415352"/>. As recorded in their article 'A case of human intersexuality having a possible XXY sex-determining mechanism';

{| align="center"| style="border"
|- align="center" | bgcolor = "DDCEF2"
|''“…There are strong grounds, both observational and genetic, for believing that human beings with chromatin-positive nuclei are genetic females having two X chromosomes. The fact that this patient is chromatin-positive and has an additional chromosome within the same size range as the X, as well as an apparently normal Y, makes it seem likely that he has the genetic constitution XXY”''<ref name="PMID13632697"><pubmed>13632697</pubmed></ref>
|}

This discovery confirmed that the Barr bodies seen in patients with KS corresponds to an extra X chromosome<ref name="PMID13632697"/>. In 1966, Harry F. Klinefelter reported that the extra X chromosome results from either meiotic nondisjunction or anaphase lag. Anaphase lag describes a chromosome which is not incorporated into the new cell in the second stage of mitosis(anaphase) due to it ‘lagging’, resulting in gametes lacking a sex chromosome <ref name="PMID3529433"><pubmed>3529433</pubmed></ref>.
The ‘prototypic’ man with KS was initially described as tall, with narrow shoulders, broad hips, sparse body hair, gynecomastia, small testes, [[#Glossary | '''androgen''']] deficiency and reduced intelligence<ref name="PMID17415352"/>. However, a few years after the syndrome was described Heller and Nelson reported that the gynacomastia was not a necessary part of the syndrome, even though it occurred in about 75% of the patients which they observed. The hallmarks of the syndrome were then thought small testes, sterility and increased excretion of follicle stimulating hormone<ref name="PMID3529433"/>. Extensive studies of these patients during their adolescence illustrated the various personality traits, which can be handled by proper counselling. Similar to today, Harry Klinefelter reported that most patients with this condition were not diagnosed until early adult life, when counselling may be less rewarding.

Below is a timeline highlighting all the major advancements and developments in Klinefelter’s Syndrome.

===Timeline===

{| style="border: solid 1px #a0a0ff"
|- align="center"
|-bgcolor="DDCEF2"
|style="width:50px"|'''Year'''
| '''Discovery'''
|-
| valign="top" bgcolor="DDCEF2"|'''1942'''
| valign="top" bgcolor="lightyellow" | Dr. Harry Klinefelter and his co-workers at Massachusetts General Hospital in Boston published a report on 9 men describing the signs and symptoms of Klinefelter’s Syndrome. The ‘prototypic’ man with Klinefelter’s syndrome was described as tall, with narrow shoulders, broad hips, sparse body hair, gynecomastia, small testes, androgen deficiency and reduced intelligence. <ref name= "PMID17415352"/>
|-

| valign="top" bgcolor="DDCEF2"|'''1949'''
| valign="top" bgcolor="lightyellow" | Barr and Bertram noticed positive [[#Glossary | '''chromatin''']] material in KS patients.It was a dense chromatin mass which they later termed, Barr body.
|-

| valign="top" bgcolor="DDCEF2"|'''1956'''
| valign="top" bgcolor="lightyellow" | The discovery of [[#Glossary | '''Barr bodies''']] as a result of the new development of Buccal smears
|-

| valign="top" bgcolor="DDCEF2"|'''1959'''
| valign="top" bgcolor="lightyellow" | Jacobs and Strong discovered that it was a chromosomal disorder, with the appearance of an extra X chromosome.
|-

| valign="top" bgcolor="DDCEF2"|'''1960s'''
| valign="top" bgcolor="lightyellow" | Development of chromosome banding techniques. <ref><pubmed>5640698</pubmed></ref>
|-

| valign="top" bgcolor="DDCEF2"|'''1962'''
| valign="top" bgcolor="lightyellow" | Maclean and Mitchell’s studies on inmates in prisons and institutions for mental health revealed an increased risk of psychiatric disorders, mental retardations and criminal behaviour in patients with Klinefelter syndrome. <ref name="PMID17415352"/>
|-

| valign="top" bgcolor="DDCEF2"|'''1966'''
| valign="top" bgcolor="lightyellow" |Dr. Harry Klinefelter reports that the extra X chromosome results from either meiotic [[#Glossary |'''non-disjunction''']] or anaphase lag. <ref name="PMID3529433"/>
|-

| valign="top" bgcolor="DDCEF2"|'''1970'''
| valign="top" bgcolor="lightyellow" | Rozen et al reported that approximately 1% of all individuals institutionalised with mental retardation have an XXY karotype. <ref><pubmed>4398603</pubmed></ref>
|-

| valign="top" bgcolor="DDCEF2"|'''1970s'''
| valign="top" bgcolor="lightyellow"| A number of centres began screening newborns for sex [[#Glossary | '''chromatin''']] abnormalities.
|-

| valign="top" bgcolor="DDCEF2"|'''1986'''
| valign="top" bgcolor="lightyellow"| Dr. Harry Klinefelter described that the hallmarks of the syndrome are now small testes, sterility and increased excretion of follicle stimulating hormone. <ref name="PMID3529433"/>

He also reported that most patients with this condition were not diagnosed until early adult life, when counselling may be less rewarding. <ref name="PMID3529433"/>

Treated hypogonadism with injected testosterone, and thought this also aided personality abnormalities in adolescent patients. <ref name="PMID3529433"/>
|-

| valign="top" bgcolor="DDCEF2"|'''1992'''
| valign="top" bgcolor="lightyellow"| The Comparative Genomic Hybridization (CGH) analysis was developed as a genome wide screening strategy for detecting DNA copy number imbalances.<ref><pubmed> 1359641</pubmed></ref> A classic array-CGH experiment is shown figure 2.
|-

| valign="top" bgcolor="DDCEF2"|'''1995'''
| valign="top" bgcolor="lightyellow"| Reiss et al., found that half all mental retardation in males originates from a defective gene on the X chromosome. Thus, the X chromosome comprises the genes involved in human cognition. <ref><pubmed>7585014</pubmed></ref>
|-

| valign="top" bgcolor="DDCEF2"|'''1998'''
| valign="top" bgcolor="lightyellow"| Smyth and Bremmer concluded that XXY karotypes occurs in 1 in 500 live male births and is the most common type of human chromosome anomaly. <ref><pubmed>9645824</pubmed></ref>

They also hypothesised that the characteristics features of Klinefelter’s syndrome originate from genes escape inactivation and are expressed in excess.
|-

| valign="top" bgcolor="DDCEF2"|'''2002'''
| valign="top" bgcolor="lightyellow"| Crow et al., suggested that at least one gene or genes in the X-Y homologous regions of the sex chromosomes which escape’s normal X- inactivation are crucial for language functioning.<ref><pubmed> 15729733</pubmed></ref>
|-

| valign="top" bgcolor="DDCEF2"|'''2010'''
| valign="top" bgcolor="lightyellow"| Stefano Gambardella et al., designed a targeted array called GOLD (gain or loss detection) Chip which detects unexpected major chromosome imbalances. <ref>Stefano G., Erika C., Francesca M., Giusy S., Francesca G., Michela B., Anna M. N., Antonio N., Ercole B., Laura B. and Giuseppe N.(2010) Design, Construction and Validation of Targeted BAC Array-Based CGH Test for Detecting the Most Commons Chromosomal Abnormalities. ‘’Genomic Insights.’’ 3:9-21</ref>
|-
|}

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==Aetiology==

Chromosome abnormalities have a high incidence in humans. The most common type is [[#Glossary | '''aneuploidy''']], which is the loss (monosomy) or gain (trisomy) of an entire chromosome <ref name="PMID12926525"><pubmed>12926525</pubmed></ref>. [[#Glossary | '''Aneuploidy''']]’s occur in approximately 5% of pregnancies which survive long enough to be seen and approximately 10-25% of all fertilised human oocytes are either monosomic or trisomic <ref name="PMID12926525"/>. Trisomies are incapable of normal development, the consequences are less severe for the sex chromosomes than the autosomes, leading to enhanced sex chromosomes among live-borns in comparison with autosomal trisomies. Therefore, the 47,XXY condition, termed Klinefelter’s Syndrome (KS) is identified in almost 1 of every 1000 male births, causing it to be one of the most commonly identified chromosome abnormality among live-born individuals.

===Non-Disjunction===

[[File:Maternal Non-Disjunction.PNG |thumb|right|230px|Figure 4. Maternal Non-disjunction]]

[[#Glossary | '''Non-disjunction''']] is the failure of chromosome pairs to separate during the first and second meiotic divisions. Maternal XXY can be caused by [[#Glossary | '''non-disjunction''']] during the first and second meiotic divisions, however, XXY of paternal origin can only occur during the first meiotic division. In the great majority of trisomies the additional chromosome is of maternal origin and results from an error during the first meiotic division as seen in figure 1. However, the 47,XXY has been extensively studied and around one half of all cases are paternally derived. The nature of the errors by which maternal and paternal XXYs can arise are extremely diverse. The process of [[#Glossary | '''meiosis''']] serves to generate haploid gametes through a specialised cell division process, consisting of two stages of cell division, MI and MII. During prophase of MI the pairs of homologous chromosomes synapse and undergo recombination, with chiasmata being formed at the sites of exchange. Their purpose is to link together the homologues and therefore play a crucial role in the proper disjunction of chromosomes in the first meiotic division<ref name="PMID12926525"/>.

[http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Meiosis%20I.htm Animation Meiotic Non-disjunction - Meiosis I]

[http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Meiosis%20II.htm Animation Meiotic Non-disjunction - Meiosis II]

===Genetics===

Although many other genes are important for proper sexual development of the male foetus, the SRY (sex-determining region of Y chromosome) gene located on the Y chromosome directs the development of the foetal gonads into testes. Typically, when two or more X chromosomes are present in a cell, as in healthy females or sex chromosome disorders like 47,XXY, only one is active. The additional X chromosome is mostly inactive and the X [[#Glossary | '''chromatin''']] is perceived as a Barr body in the periphery of the cell nucleus<ref name=PMID"21521364"<pubmed>21521364</pubmed></ref>.
In addition to specific regions, both sex chromosomes carry short regions of homology termed pseudoautosomal regions (PAR) <ref><pubmed> 20228051</pubmed></ref> which remain active in men and woman <ref name="PMID21521364"/>. They behave as an autosome and function to allow X and Y chromosomes to pair and properly segregate during [[#Glossary | '''meiosis''']] in males. Some genes in the X chromosome which are not homologous to the Y chromosome can escape inactivation and are functionally duplicated in KS males<ref name="PMID21521364"><pubmed>21521364</pubmed></ref>.

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I also found this image for the introduction. [[File:47,XXY Klinefelter's Syndrome.jpg|thumb|right|220px|47,XXY Klinefelter's Syndrome]]

User talk:Z3289829 - Revision history

Z3289829: Created page with "'''Reason for low contribution in Group 3 project: Klinefelter's Syndrome''' The reason may be due to me uploading my work in chunks. Below is my contributions to two sections ..."