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Ccoatsworth.
Wiki Education Foundation-supported course assignment
This article is or was the subject of a Wiki Education Foundation-supported course assignment. Further details are available
on the course page. Student editor(s):
Nicolef004.
This article is being expanded by Ccoatsworth as part of the course Biology 3595A: Advanced Genetics at The University of Western Ontario.
Ccoatsworth (
talk)
21:47, 15 October 2015 (UTC)reply
Chromosomal deletion syndromes result from
deletion of segments of
chromosomes. Deletion in excess of 2% of original DNA mass usually result in death/abortion of
Zygote. Smaller deletions result in
Microdeletion syndrome, which are detected using
fluorescence in situ hybridization (FISH). Large-scale deletions (>5 Mb) not resulting in death tend to result in Chromosomal deletion syndromes. Deletions of this magnitude are visible using
karyotyping techniques.
Expand on the opening summary.
larger deletion --> specific range of deletion sizes
how it's done/detected/mapped
type of equipment used (how powerful the microscopes need to be)
The chromosomal basis of WHS consists of a deletion of the most terminal portion of the short arm of chromosome 4. The deleted segment of reported individuals represent about one half of the p arm, occurring distal to the bands 4p15.1-p15.2.
Many reports are particularly striking in the appearance of the craniofacial structure (prominent forehead, hypertelorism, the wide bridge of the nose continuing to the forehead) which has led to the descriptive term “Greek warrior helmet appearance”.
The proximal boundary of the WHSCR was defined by a 1.9 megabase terminal deletion of 4p16.3 that includes the proposed candidate genes LEMT1 and WHSC1. This was identified by two individuals that exhibited all 4 components of the core WHS phenotype, which allowed scientists to trace the loci of the deleted genes.
There is wide evidence that the WHS core phenotype (growth delay, intellectual disability, seizures, and distinctive craniofacial features) is due to haploinsufficiency of several closely linked genes as opposed to a single gene. Related genes that impact variation include:
WHSC2 (also known as NELF-A) is involved in multiple aspects of mRNA processing and the cell cycle
SLBP, a gene encoding Stem Loop Binding Protein, resides telomeric to WHSC2, and plays a crucial role in regulating histone synthesis and availability during S phase
LETM1 has initially been proposed as a candidate gene for seizures; it functions in ion exchange with potential roles in cell signaling and energy production.
FGFRL1, encoding a putative fibroblast growth factor decoy receptor, has been implicated in the craniofacial phenotype and potentially other skeletal features, and short stature of WHS
CPLX1 has lately been suggested as a potential candidate gene for epilepsy in WHS
PIGG gene (Phosphotidilinositol glycan anchor biosynthesis, class G), involved in the biogenesis of GPI anchor proteins, has recently been implicated in the occurrence of seizures
WHSC1 spans a 90-kb genomic region, two-thirds of which maps in the telomeric end of the WHCR; WHSC1 may play a significant role in normal development. Its deletion likely contributes to the WHS phenotype. However, variation in severity and phenotype of WHS suggests possible roles for genes that lie proximally and distally to the WHSCR
5p deletions
With an incidence of 1 in 15,000 to 1 in 50,000 live births, it is suggested to be one of the most common contiguous gene deletion disorders.
5p deletions, whether terminal or interstitial, occur at different breakpoints; the variability seen among individuals may be attributed to the differences in their genotypes.
Individuals that make up the population of those affected by 5p deletions comprise the 5p Minus Society, an online family support group in the United States
5p deletions are most commonly de novo occurrences, which are paternal in origin in 80–90% of cases, possibly arising from chromosome breakage during gamete formation in males
There is no specific correlation found between size of deletion and severity of clinical features because the results vary so widely
Some examples of the possible dysmorphic features include: downslanting palpebral fissures, broad nasal bridge,microcephaly, low-set ears, preauricular tags, round facies, short neck, micrognathia, and dental malocclusionhypertelorism, epicanthal folds, downturned corners of the mouth
Nicolef004 (
talk)
05:10, 4 November 2015 (UTC)reply