User:Rahaf M Hassan91/sandbox

I am evaluating this page "petite mutation": the petite mutation is an interesting topic to work with.The topic is related to the content of the article. But I feel like it needs more pictures and to identify the link to diseases. Also, maybe a figure explaining the Experiment section. at last, more References. Over all, nice job. Rahaf M Hassan91 (talk) 21:24, 8 September 2018 (UTC) Petite_mutation

Uner Tan syndrome From Wikipedia, the free encyclopedia Jump to navigationJump to search Uner Tan syndrome, Unertan syndrome or UTS is a syndrome proposed by the Turkish evolutionary biologist Üner Tan. According to Tan, persons affected by this syndrome walk with a quadrupedal locomotion and are afflicted with "primitive" speech and severe mental retardation. Tan postulated that this is an example of "reverse evolution".[1] The proposed syndrome was featured in the 2006 BBC2 documentary The Family That Walks On All Fours.

Contents 1	History 2	Genetics 3	Criticism 4	See also 5	References 6	Further reading History The Ulaş family of nineteen from rural southern Turkey has been the primary example of the proposed syndrome. Tan described five members as walking with a quadrupedal gait using their feet and the palms of their hands. In infants, where this is a rare but a normal stage prior and sometimes following bipedal walking, such a gait is called "bear crawl". The affected family members are also severely mentally retarded and their speech is affected. Tan proposed that these are symptoms of Uner Tan syndrome.[1]

In January 2008, Tan reported on another family (four males and two females) located in southern Turkey.[2]

Four other unrelated cases in families are described as having various degrees of UTS.[2] Males may be affected more than females. It is also claimed[who?] that some individuals are unaware of time, lack language, have severe mental retardation with no conscious experience, and communicate by using sounds.[clarification needed] Two males are unable to stand up, while in other cases, can stand up but cannot make a step when standing. Less severe cases use toe walking, which is a normal phase in child gait development.

Genetics Uner Tan syndrome has been linked to intrafamilial marriage and reproduction, which suggests that it is an autosomal recessive disorder.[3] The main characteristic of this syndrome is habitual quadrupedalism, meaning they can stand up straight until they try to move, then they walk on their hands and knees. According to Tan, the syndrome may be placed in its own category under types of cerebellar ataxias.[3] This simply means it is a type of disorder that involves the cerebellum becoming inflamed, resulting in lack of control of voluntary movements.[4] Uner Tan syndrome falls into this category because it has similar symptoms to other cerebellar ataxia disorders such as Disequilibrium Syndrome (DES-H) and Cayman Syndrome. These symptoms include dysarthria, nystagmus, and hypoplasia of the cerebellum and vermis.[3]

Human geneticist Tayfun Ozcelik discovered homozygosity in a region on chromosome 9p24 in Uner Tan syndrome individuals.[1] The very low density lipoprotein receptor gene (VLDLR) is located in this region, which is involved in the migration of neuroblasts within the brain. Ozcelik found mutations in the VLDRL gene in affected individuals, and suggested that these specific mutations may lead to VLDRL deficiency during the development of the brain. This may affect the proper formation of cerebrocerebellar structures critical for upright walking, resulting in quadrupedal locomotion.[1] Other genes may also be involved in habitual quadrupedalism. For example, in some affected families, chromosome 17p13 was involved, while in other families 17p13 and 9p24 had no effect. This suggests the syndrome is genetically heterogeneous.[5]

The researchers took a different approach to isolate the gene that causes this syndrome by comparing the genealogy of all the families in which the syndrome had been reported. The two types of Uner Turner Syndrome, UTS type I and type II show genetic heterogeneity. In two of the first families (Antep and Canakkale families) it was the VLDLR gene on chromosome 9p24. This is the only family so far to express homozygocity. It is possible for dissimilar mutations in the VLDLR gene to result in the same phenotype as a result of allelic heterogeneity. In the Iskenderun family, a different gene, WDR81 on chromosome 17p13.1-13.3 was isolated. The Iraqi family had CA8 on chromosome 8q isolated. In the last family studied (the Adana family), the researchers were not able to isolate any gene, only a locus on chromosome 13q. This isolation led to the implication of more genes as the causes of quadrupedalism. The fact that chromosome 9p24 had no effect on some families points to the genetic heterogeneity of the syndrome Rahaf M Hassan91 (talk) 08:54, 11 October 2018 (UTC).

Another approach for establishing the genealogy has been to compare UTS with similar syndromes such as disequilibrium syndrome (DES) and Joubert syndrome. UTS seems to be genetically different from DES in that DES can be linked to a single gene, VLDLR, located on chromosome 9p24. When compared with DES, Joubert syndrome has shown links to 7 gene mutations. As is the case with almost all diseases, the three syndromes compared show alleic heterogeneity Rahaf M Hassan91 (talk) 08:54, 11 October 2018 (UTC).

Researchers recently isolated a recessive TUBB2B mutation in one of the families diagnosed with UTS. This makes TUBB2B the fifth gene after VLDLR, WDR81, CA8 and ATP8A2, associated with this syndrome. Patients with mutations of TUBB2B are phenotypically similar to those with VLDLR, WDR81 and ATP8A2 mutations. The researchers proposed a tentative reclassification of UTS into three types based on how they present themselves clinically. They attribute the first type (referred to as developmental UTS) to mutations in TUBB2B and VLDLR. Type II (degenerative UTS) is linked to ATP8A2 and WDR81 while type III (UTS without cerebral malformations) implicates CA8 Rahaf M Hassan91 (talk) 08:54, 11 October 2018 (UTC).

The problem with identifying the specific mutation that leads to Uner Tan syndrome is the fact that different mutations in a single gene can lead to a wide range of phenotypes. In the VLDLR gene, similar mutations may be responsible for different types of cerebellar ataxias that affect proper locomotion in humans.[3]

Criticism Neuroscientist and evolutionary psychologist Roger Keynes, psychologist Nicholas Humphrey and medical scientist John Skoyles have argued that the gait of these individuals is due to two rare phenomena coming together, not atavism.[6] First, instead of initially crawling as infants on their knees, they started off learning to move around with a "bear crawl" on their feet.[6] Second, due to their congenital brain impairment, they found balancing on two legs difficult.[6] Because of this, their motor development was channeled into turning their bear crawl into a substitute for bipedalism.[6]

Uner Tan and colleagues claim that UTS differs from disequilibrium syndrome [2]

It's terribly easy to be led away by some notion of living fossils...I'm not going to make any bones about this. I think that Professor Tan's description of this family as a "devolution," as an evolutionary throwback, is not only scientifically irresponsible, but is deeply insulting to this family.

— Professor Nicholas Humphrey, The Family That Walks On All Fours See also The Family That Walks On All Fours, documentary about the Ulas family VLDLR-associated cerebellar hypoplasia References

Tan U (March 2006). "A new syndrome with quadrupedal gait, primitive speech, and severe mental retardation as a live model for human evolution". The International Journal of Neuroscience. 116 (3): 361–9. doi:10.1080/00207450500455330. PMID 16484061. Tan U, Karaca S, Tan M, Yilmaz B, Bagci NK, Ozkur A, Pence S (January 2008). "Unertan syndrome: a case series demonstrating human devolution". The International Journal of Neuroscience. 118 (1): 1–25. doi:10.1080/00207450701667857. PMID 18041603. Ozcelik T, Akarsu N, Uz E, Caglayan S, Gulsuner S, Onat OE, Tan M, Tan U (March 2008). "Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans". Proceedings of the National Academy of Sciences of the United States of America. 105 (11): 4232–6. doi:10.1073/pnas.0710010105. PMC 2393756. PMID 18326629. Schmahmann JD (August 2004). "Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome". The Journal of Neuropsychiatry and Clinical Neurosciences. 16 (3): 367–78. doi:10.1176/jnp.16.3.367. PMID 15377747. Onat OE, Gulsuner S, Bilguvar K, Nazli Basak A, Topaloglu H, Tan M, Tan U, Gunel M, Ozcelik T (March 2013). "Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion". European Journal of Human Genetics. 21 (3): 281–5. doi:10.1038/ejhg.2012.170. PMID 22892528. Humphrey N, Keynes R, Skoyles JR (2005). "Hand-walkers: five siblings who never stood up" (PDF). Discussion Paper. London, UK: Centre for Philosophy of Natural and Social Science.

Further reading Tan U (July 2010). "Uner tan syndrome: history, clinical evaluations, genetics, and the dynamics of human quadrupedalism". The Open Neurology Journal. 4: 78–89. doi:10.2174/1874205X01004010078. PMC 3024602. PMID 21258577. Tan U (2012). "Development of bipedal and quadrupedal locomotion in humans from a dynamical systems perspective.". In Seidl-De-Moura ML. Human Development; Different Perspectives. Croatia: InTech Publications. pp. 43–62. doi:10.5772/36667. ISBN 978-953-51-0610-4. Tan U, Tamam Y, Karaca S, Tan M (2012). "Uner Tan syndrome: review and emergence of human quadrupedalism in self-organization, attractors and evolutionary perspectives.". In Tan U. Latest Findings in Intellectual and Developmental Disabilities Research. Croatia: InTech Publications. pp. 1–44. doi:10.5772/28675. ISBN 978-953-307-865-6.