A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Habib, Abdella M.; Matsuyama, Ayako; Okorokov, Andrei L.; Santana-Varela, Sonia; Brás, José; Aloisi, Anna Maria; Emery, Edward C.; Bogdanov, Yury; Follenfant, Maryne; Gossage, Sam J; Gras, Mathilde; Humphrey, Jack; Kolesnikov, Anna; Cann, Kim Le; Li, Shengnan; Minett, Michael S.; Pereira, Vanessa; Ponsolles, Clara; Sikandar, Shafaq; Torres, Juan Antonio Vera; Yamaoka, Kiwamu; Zhao, Jing; Komine, Yuriko; Yamamori, Tetsuo; Maniatis, Nikolas; Panov, Kostya I.; Houlden, Henry; Ramirez, Juan D.; Bennett, David L.H.; Marsili, Letizia; Bachiocco, Valeria; Wood, John N.; Cox, James J.

doi:10.1093/brain/awx326

Cited by 43 publications

(29 citation statements)

References 49 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the regions under putative selection we looked for genes that could be related to adaption of Russian sheep breeds to local environments ( Table 2). We noticed that five breeds: Karachaev, Krasnoyarsk, Lezgin, Salsk, and Altai Mountain had a common signature of selection reported by the DCMS method near the ZFHX2 (zinc finger homeobox 2), a gene which was shown to be responsible for an inability to feel pain in humans (including low and high temperatures) [26]. The same authors report that ZFHX2 knock-out mice had significantly higher acute thermal pain thresholds [26].…”

Section: Candidate Genes For Adaptation Of the Russian Sheep Breeds Tmentioning

confidence: 96%

High-density genotyping reveals signatures of selection related to acclimation and economically important traits in 15 local sheep breeds from Russia

et al. 2019

View full text Add to dashboard Cite

Background: Domestication and centuries of selective breeding have changed genomes of sheep breeds to respond to environmental challenges and human needs. The genomes of local breeds, therefore, are valuable sources of genomic variants to be used to understand mechanisms of response to adaptation and artificial selection. As a step toward this we performed a high-density genotyping and comprehensive scans for signatures of selection in the genomes from 15 local sheep breeds reared across Russia. Results: Results demonstrated that the genomes of Russian sheep breeds contain multiple regions under putative selection. More than 50% of these regions matched with intervals identified in previous scans for selective sweeps in sheep genomes. These regions contain well-known candidate genes related to morphology, adaptation, and domestication (e.g., KITLG, KIT, MITF, and MC1R), wool quality and quantity (e.g., DSG@, DSC@, and KRT@), growth and feed intake (e.g., HOXA@, HOXC@, LCORL, NCAPG, LAP3, and CCSER1), reproduction (e.g., CMTM6, HTRA1, GNAQ, UBQLN1, and IFT88), and milk-related traits (e.g., ABCG2, SPP1, ACSS1, and ACSS2). In addition, multiple genes that are putatively related to environmental adaptations were top-ranked in selected intervals (e.g., EGFR, HSPH1, NMUR1, EDNRB, PRL, TSHR, and ADAMTS5). Moreover, we observed that multiple key genes involved in human hereditary sensory and autonomic neuropathies, and genetic disorders accompanied with an inability to feel pain and environmental temperatures, were top-ranked in multiple or individual sheep breeds from Russia pointing to a possible mechanism of adaptation to harsh climatic conditions.

show abstract

Section: Candidate Genes For Adaptation Of the Russian Sheep Breeds Tmentioning

confidence: 96%

High-density genotyping reveals signatures of selection related to acclimation and economically important traits in 15 local sheep breeds from Russia

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Interestingly, a recent study found a pain insensitivity disorder caused by a mutation in ZFHX2 (Habib et al 2017), which carries an AHMC, and three HHMCs are observed in NPAP1, which might be associated with the Prader-Willi syndrome, involving behavioral problems and a high pain threshold (Buiting et al 2007). Such changes may point to differences in levels of resilience to pain between Neanderthals and modern humans.…”

Section: Life History and Other Phenotypic Traitsmentioning

confidence: 99%

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

Kuhlwilm

Boeckx

2018

Preprint

View full text Add to dashboard Cite

10Throughout the past decade, studying ancient genomes provided unique insights into human 11 prehistory, and differences between modern humans and other branches like Neanderthals can 12 enrich our understanding of the molecular basis of the human condition. Modern human variation 13 and the interactions between different hominin lineages are now well studied, making it reasonable 14 to explore changes that are observed at high frequency in present-day humans, but do not reach 15 fixation. Here, we put forward interpretation of putative single nucleotide changes in recent modern 16 human history, focusing on 571 genes with non-synonymous changes at high frequency. We 17 suggest that molecular mechanisms in cell division and networks affecting cellular features of 18 neurons were prominently modified by these changes. Complex phenotypes in brain growth 19 trajectory and cognitive traits are likely influenced by these networks and other changes presented 20here. We propose that at least some of these changes contributed to uniquely human traits.

show abstract

“…This congenital hypoalgesia is a rare inherited disorder. A human pain insensitivity disorder is caused by a point mutation in ZFHX2 gene (Habib et al, 2018). There is no peripheral neuropathy in the family.…”

Section: Zfhx2 Genementioning

confidence: 99%

A Review of the Relationship among Self, Mind and Brain in Functional Magnetic Resonance Imaging Study: Tree-Pattern Image of Semantic Map in Human Brain Viewed from the Ultron-Logotron Theory

Chung¹

2018

OJPP

View full text Add to dashboard Cite

The scientific relationship among self, mind and brain is still not clearly known. Self's subjective experience of perception and cognition of words, feelings, thoughts etc. is supported by the integrity of human brain. Consequently, neuroscientists, psychologists, psychiatrists, physicists and philosophers have been investigating to find the scientific relationship between mind and brain, consciousness and quantum physics. Recent experimental evidence suggests that the neural correlate of consciousness is located in certain parts of the cortico-thalamic system. But it is not known specifically which parts of the human brain are involved in the human cognitive activity. In this study, the author proposed a tree-pattern architecture of the cerebral neural substrate in cognitive understanding of words, feelings, and thoughts on the basis of the author's hypothesis of the ultron-logotron theory to explain the neural correlate of consciousness.

show abstract

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Cited by 43 publications

References 49 publications

High-density genotyping reveals signatures of selection related to acclimation and economically important traits in 15 local sheep breeds from Russia

High-density genotyping reveals signatures of selection related to acclimation and economically important traits in 15 local sheep breeds from Russia

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

A Review of the Relationship among Self, Mind and Brain in Functional Magnetic Resonance Imaging Study: Tree-Pattern Image of Semantic Map in Human Brain Viewed from the Ultron-Logotron Theory

Contact Info

Product

Resources

About