Cis-Regulatory Enhancer Mutations are a Cause of Human Limb Malformations

2012 ◽  
pp. 73-93
Author(s):  
Julia E. VanderMeer ◽  
Nadav Ahituv
Keyword(s):  
Limb Malformations ◽  
Human Limb

FGFs, their receptors, and human limb malformations: Clinical and molecular correlations

2002 ◽  
Vol 112 (3) ◽  
pp. 266-278 ◽  
Author(s):  
Andrew O.M. Wilkie ◽  
Susannah J. Patey ◽  
Shih-hsin Kan ◽  
Ans M.W. van den Ouweland ◽  
Ben C.J. Hamel
Keyword(s):  
Limb Malformations ◽  
Human Limb

scholarly journals Mutations in gene regulatory elements linked to human limb malformations

2019 ◽  
Vol 57 (6) ◽  
pp. 361-370
Author(s):  
Karol Nowosad ◽  
Ewa Hordyjewska-Kowalczyk ◽  
Przemko Tylzanowski
Keyword(s):  
Regulatory Elements ◽  
Regulatory Function ◽  
Protein Coding ◽  
Coding Regions ◽  
Technological Advances ◽  
Non Coding Rna ◽  
Limb Malformations ◽  
Gene Regulatory Elements ◽  
Chromatin Organisation ◽  
Human Limb

Most of the human genome has a regulatory function in gene expression. The technological progress made in recent years permitted the revision of old and discovery of new mutations outside of the protein-coding regions that do affect human limb morphology. Steadily increasing discovery rate of such mutations suggests that until now the largely neglected part of the genome rises to its well-deserved prominence. In this review, we describe the recent technological advances permitting this unprecedented advance in identifying non-coding mutations. We especially focus on the mutations in cis-regulatory elements such as enhancers, and trans-regulatory elements such as miRNA and long non-coding RNA, linked to hereditary or inborn limb defects. We also discuss the role of chromatin organisation and enhancer–promoter interactions in the aetiology of limb malformations.

scholarly journals Why study human limb malformations?

2003 ◽  
Vol 202 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Andrew O. M. Wilkie
Keyword(s):  
Limb Malformations ◽  
Human Limb

Extent of Duplication in Lower-Limb Malformations Suggests the Time of the Teratogenic Insult

PEDIATRICS ◽  
1993 ◽  
Vol 91 (2) ◽  
pp. 411-413
Author(s):  
David S. Packard ◽  
E. Mark Levinsohn ◽  
David R. Hootnick
Keyword(s):  
Lower Limb ◽  
Limb Development ◽  
Lower Limbs ◽  
Relative Time ◽  
Vertebrate Limb ◽  
The Future ◽  
Vertebrate Limb Development ◽  
Limb Malformations ◽  
Human Limb ◽  
Limb Specification

Investigations of vertebrate limb development have suggested that a process called "specification" instructs the cells of the future limb as to which tissues they should form. This process proceeds in a wave-like manner, starting at the most proximal levels of the future limb and ending at its distal tip. Human limb specification probably occurs during the fourth and fifth weeks of development. It is proposed that human limb duplications result from errors of specification and, furthermore, that the more distal the duplication, the later the occurrence of the teratogenic event during the specification process. Therefore, among human lower limbs with duplications, one may be able to estimate the relative time of the teratogenic event by comparing the levels at which the duplications occur.

scholarly journals cis-regulatory mutations are a genetic cause of human limb malformations

2011 ◽  
Vol 240 (5) ◽  
pp. 920-930 ◽  
Author(s):  
Julia E. VanderMeer ◽  
Nadav Ahituv
Keyword(s):  
Regulatory Mutations ◽  
Limb Malformations ◽  
Human Limb

Implementation and Calibration of Real Time Posture Tracking Of Human Limb Segment Motions

2006 ◽  
Vol 2 (1) ◽  
pp. 50-56
Author(s):  
N. Suthanthira Vanitha ◽  
◽  
V. Palanisamy ◽  
M. Mani
Keyword(s):  
Real Time ◽  
Limb Segment ◽  
Human Limb ◽  
Posture Tracking

Greig Cephalopolysyndactyly Syndrome: Phenotypic Variability Associated with Variants in Two Different Domains of GLI3

2020 ◽  
Author(s):  
Hammal Khan ◽  
Sohail Ahmed ◽  
Sadia Nawaz ◽  
Wasim Ahmad ◽  
Muhammad Arshad Rafiq ◽  
...  
Keyword(s):  
Skeletal Development ◽  
Phenotypic Variability ◽  
Transcriptional Regulator ◽  
Molecular Study ◽  
Inherited Disorders ◽  
Pakistani Population ◽  
Greig Cephalopolysyndactyly Syndrome ◽  
Novel Variants ◽  
Limb Malformations ◽  
Pleiotropic Gene

Abstract Background GLI3 is a transcriptional regulator of several genes involved in mammalian skeletal development. Mutations in the pleiotropic gene GLI3 may result in different inherited disorders including Greig cephalopolysyndactyly syndrome (GCPS). GCPS is characterized by mild to severe craniofacial and limb malformations. Methods and Results Here, we report clinical and molecular study of 3 families with GCPS originated in different regions of Pakistan. Sanger sequencing revealed two novel variants including a frameshift [c. 3790_3791InsC, p.(Gly1236Argfs*11)] and a missense [c.1692A>G, p.(His536Arg)], and one previously reported variant [c.1965_1966delAT, p.(His627Glufs*48)] located in 2 different domains of the GLI3. Conclusion This study not only expanded spectrum of the mutations in the GLI3 but also highlighted phenotypic variability in the GCPS patients. This will facilitate diagnosis and genetic counseling of families with same and related disorders in the Pakistani population.

Hybrid Control of the Berkeley Lower Extremity Exoskeleton (BLEEX)

2005 ◽  
Author(s):  
Lihua Huang ◽  
Ryan Ryan Steger ◽  
H. Kazerooni
Keyword(s):  
Position Control ◽  
Hybrid Control ◽  
System Sensitivity ◽  
Walking Gait ◽  
Mixed Control ◽  
Stance Control ◽  
Control Scheme ◽  
Load Carrying ◽  
Human Limb ◽  
Careful Design

The first functional load-carrying and energetically autonomous exoskeleton was demonstrated at U.C. Berkeley, walking at the average speed of 0.9 m/s (2 mph) while carrying a 34 kg (75 lb) payload. The original BLEEX sensitivity amplification controller, based on positive feedback, was designed to increase the closed loop system sensitivity to its wearer’s forces and torques without any direct measurement from the wearer. The controller was successful at allowing natural and unobstructed load support for the pilot. This article presents an improved control scheme we call “mixed” control that adds robustness to changing BLEEX backpack payload. The walking gait cycle is divided into stance control and swing control phases. Position control is used for the BLEEX stance leg (including torso and backpack) and the sensitivity amplification controller is used for the swing leg. The controller is also designed to smoothly transitions between these two schemes as the pilot walks. With mixed control, the controller does not require a good model of the BLEEX torso and payload, which is difficult to obtain and subject to change as payload is added and removed. As a tradeoff, the position control used in this method requires the human to wear seven inclinometers to measure human limb and torso angles. These additional sensors require careful design to securely fasten them to the human and increase the time to don (and doff) BLEEX.

Effects of the teratogenic folic acid antagonist, 9-methyl pteroylglutamic acid, on hydroxyproline levels in fetal rat limbs

Development ◽  
1977 ◽  
Vol 41 (1) ◽  
pp. 289-294
Author(s):  
R. R. Schmidt ◽  
K. P. Chepenik ◽  
B. V. Paynton
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Total Body Weight ◽  
Pregnant Rats ◽  
Skeletal Malformations ◽  
Fetal Rat ◽  
Pteroylglutamic Acid ◽  
Limb Malformations ◽  
Total Body ◽  
Rate Of Accumulation

Pregnant rats were subjected to either a folic-acid-deficient regimen that produces multiple congenital skeletal malformations, or a control folic-acid-supplemented regimen. Fetal limbs were extirpated on days 16 and 18 of gestation, pooled from each litter, homogenized, and aliquots set aside for hydroxyproline, protein and DNA determinations. We found that (1) the amount of protein recovered per treated limb was approximately half that of controls on both days, (2) the amount of protein recovered per treated or controlday-18 limb was twice that of a day-16 limb, (3) treated limbs constituted the same percentage of total body weight as in controls on day 16, but a smaller percentage than in controls on day 18, and (4) the concentration of hydroxyproline (μg/mg protein) was significantly less for treated limbs than for controls on day 18 of gestation. We noted also that: (1) lowest hydroxyproline concentrations were found in limbs from treated fetuses with gross limb malformations, (2) intermediate concentrations were found in limbs of treated fetuses not exhibiting gross limb malformations, and (3) highest concentrations were found in control limbs. We suggest that the treatment resulted in (1) a decreased rate of accumulation of protein in limbs prior to day 16, but not from day 16 to day 18, (2) a decreased rate of accumulation of some non-protein component(s) in treated limbs from day 16 to day 18, and (3) an altered collagen metabolism.

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