Chromosome+8

=__Chromosome #8__=

__**Size: **__
Chromosome 8 has 146 million base pairs. It represents about 4.5 to 5% of total DNA in cells. It has between 700 to 1,100 genes.(**[|1]) ** (Chromosome,n.d.)

** Excerpt from __Genome__ by Matt Ridley **
"So far, each chapter of this book has concentrated on a gene or genes tacitly assuming that they are the things that matter in the genome. Genes, remember, are stretches of DNA that comprise the recipe for proteins. But ninety-seven per cent of our genome does not consist of true genes at all. It consists of a menagerie of entities called pseudogenes, retropseudogenes, satellites, minisatellites, microsatellites, transposons, and retrotransposons: all collectively known as 'junk DNA', or sometimes, probably more accurately, as 'selfish DNA'. Some of these are genes of a special kind, but most are just chunks of DNA that are never transcribed into the language of protein. Since the story of this stuff follows naturally from the tale of sexual conflict related in the last chapter, this chapter will be devoted to junk DNA. Fortunately, this is a good place to tell the story, because I have nothing more particular to say about chromosome 8. That is not to imply that it is a boring chromosome, or that it possesses a few genes, just that none of the genes yet found on chromosome 8 has caught my rather impatient attention. (For its size, chromosome 8 has been relatively neglected, and is one of the least mapped chromosomes.)"__** 10 (Ridley, 1999, p.124) **__

__Gene 1:__ ANK1 gene- officially known as ankyrin 1, erthrocytic


__** Scientific Terms: **__ The ANK1 gene provides instruction for making a protein called ankyrin-1. The cytogenic location of this gene is at 8p11.1. To be more precise, the molecular location of this gene is base pairs 41,510,743 to 41,754,279. This protein is primarily active in red blood cells, but it is also found in muscle and brain cells. In red blood cells, ankyrin-1 is located at the cell membrane, where it attaches to other membrane proteins. The binding of membrane proteins to one another maintains the stability and structure of red blood cells but also allows for their flexibility. The proteins allows the cell to change shape without breaking when passing through narrow blood vessels. In muscle and brain cells, ankyrin-1 performs similar functions, binding to other membrane proteins to play a role in cell stability, cell movement, and other cell functions.(__** [|4]) **__** ( **ANK1, n.d.)

__** Layman's Terms: **__ The joining of proteins keep the red blood cell's structure stable, and it keeps the cell flexible. If the proteins were not there, then the red blood cell would break while passing through the blood vessels.The proteins also let the cell change its shape while passing through extremely narrow blood vessels, which are basically passages that blood cells flow through. Ankyrin-1 also does the same thing for muscle and brain cells. It keeps these cells stable and is important to cell movement.Without this gene, then this very important protein would not be produced causing blood to break while passing through blood vessels, which would lead to blood cell shortages, also known as anemia. An individual can die from blood shortages. A disorder related to a change or lack of ANK1 is called hereditary spherocytosis.
 * Location of Gene: 8p11.1
 * This gene is located on the shorter arm of the chromosome, which is p, and it's position is 11.1.[[image:hellerbrittani/spherocytosis.jpg width="302" height="199" align="right" caption="Hereditary Spherocytosis"]]
 * Function of ANK1: instructions for production of protein, ankyrin 1
 * Protein, ankyrin 1, is found in red blood cells.
 * Also found in muscle and brain cells
 * In red blood cells - protein found on cell membrane
 * Ankyrin 1 (protein) joins with other proteins found on the cell membrane
 * Joining of proteins = Good, Important, and Necessary

__** Gene 2: **__ WRN gene- officially known as Werner syndrome, RecQ helicase-like
__** Scientific Terms: **__ The Werner syndrome protein (WRN) is a member of the human RecQ family DNA helicases implicated in the maintenance of genome stability.The WRN gene provides instructions for producing the Werner protein. WRN plays a crucial role in the response to replication stress and significantly contributes to the recovery of stalled replication forks, although how this function is regulated is not fully appreciated. There is a growing body of evidence that WRN accomplishes its task in close connection with the replication checkpoint. In eukaryotic cells, the replication checkpoint response, which involves both the ATR and ATM kinase activities, is deputed to the maintenance of fork integrity and re-establishment of fork progression. Our recent findings indicate that ATR and ATM modulate WRN function at defined steps of the response to replication fork arrest.([|3]) (The Werner, n.d.)  The Werner protein functions as a type of enzyme called a helicase. Helicase enzymes generally unwind and separate double-stranded DNA.([|6]) (DNA, n.d.) The Werner protein also functions as an enzyme called an exonuclease. Exonucleases trim the broken ends of damaged DNA by removing DNA building blocks (nucleotides). Exonucleases can act as proofreaders during DNA polymerisation in DNA replication, to remove unusual DNA structures that arise from problems with DNA replication fork progression, and they can be directly involved in repairing damaged DNA.([|7]) (The role, n.d.) Research suggests that the Werner protein first unwinds the DNA and then removes abnormal DNA structures that have been accidentally generated. The cytogenic location of this gene is 8p12. Its molecular location is base pairs 30,890,777 to 31,031,276.([|5]) (WRN, n.d.) __** Layman's Terms: **__ Mutations in WRN can lead to Werner syndrome where the Werner protein is nonfunctional which results in disrupted DNA replication, repair, and transcription. The loss of this protein also results in symptoms of premature aging after puberty.
 * Location: 8p12
 * The gene is located on the short arm of the chromosome, p, and its position is 12.
 * Function of WRN: instructions for making the Werner protein
 * __ Why is this important? __**
 * The Werner protein performs two jobs. It works as an enzyme known as helicase and as exonuclease. Helicase is used during DNA replication because it unwinds DNA's double helix so that other enzymes can add complementary nucleotides to the single stranded DNA. Exonuclease removes nucleotides of DNA molecule that are damaged or wrong. It basically proofreads the DNA molecule after replication to make sure everything is in check.
 * The Werner protein unwinds the DNA (like helicase), and proofreads it (like exonuclease).
 * It deletes and removes DNA structures, nucleotides, that were copied by DNA polymerase.
 * The Werner protein keeps the structure and DNA sequences the same.
 * Without protein, then there would be many mistakes in the DNA sequences, and during DNA replication.
 * The protein is also useful during transcription, when proteins are made.

__ Disorder: Pfeiffer Syndrome __


Pfeiffer Syndrome is a genetic disorder that is caused by mutations in FGFR1 gene of FGFR2 gene. There are three types of Pfeiffer Syndrome. Type 1 is caused by either a mutation on the FGFR1 or FGFR2 genes. Types 2 and 3 is caused by mutations on the FGFR2 gene. FGFR stands for fibroblast growth factor receptor (.[|8]) (Pfeiffer,n.d.)

__**Age of onset**__: Birth, but it is usually detected in the newborn period or later.

__** How Common: **__ 1 in 100,000 individuals are affected by Pfeiffer Syndrome

__** Symptoms/Characteristics of Pfeiffer Syndrome: **__
 * Thumbs and great toes are wide and bend away from other fingers/toes[[image:hellerbrittani/Type1Pfeiffer.jpg align="right" caption="Kayleigh is 22 and has Type 1 Pfeiffer Syndrome"]]
 * Extremely short fingers and toes
 * Some webbing between the fingers/toes
 * Hearing loss
 * Dental problems
 * Visual problems sometimes occur.
 * Bulging wide-set eyes
 * Wide head; high forehead
 * Underdeveloped upper jaw
 * Beaked nose
 * Craniosynostosis - the process of early fusing of soft spots (fibrous joints) of the bones of the skull ([|9]) (A Publication, n.d.)
 * Abnormal/Asymmetric growth of skull and face
 * Severe craniosynostosis can result in developmental delays, mental retardation, seizures, or blindness. (This is usually found in Types 2 and 3 of Pfeiffer Syndrome.)

The symptoms also depend on the type of Pfeiffer Syndrome that the individual has. In Type 2 Pfeiffer Syndrome, the individual may have fused elbow and knee joints, severe visual problems, a clover-leaf shaped skull, limited brain growth, and severe mental retardation. In both Types 2 and 3, the individual may have problems with his nervous system.

__** Lethal: **__ It depends on the type of Pfeiffer Syndrome that the individual has. If an individual has Type 1 Pfeiffer Syndrome, he has a normal intelligence with a normal life span. Infants with physical abnormalities associated with Type 2 and Type 3 Pfeiffer's Syndrome can lead to life threatening complications without proper treatment.

__** How it is inherited: **__ It is an autosomal dominant trait. This means that the allele to pass on this trait is dominant and only one dominant allele is necessary to pass on this trait.

__** How it is diagnosed: **__ Pfeiffer Syndrome is diagnosed based on the presence of early fusing of bones of the skull as well as the presence of broad short thumbs and toes. During diagnosis, other syndromes are also considered. More often than not, Pfeiffer Syndrome is diagnosed during newborn months because it is very hard to diagnose through ultrasounds, and signs of Pfeiffer Syndrome vary greatly. It may not be shown in an ultrasound. ([|9]) (A Publication, n.d.)

__** Treatments: **__ There is no treatment for the eradication of Pfeiffer Syndrome, but multiple surgeries from one's specialized care team of physicians will determine what best suits and helps one's child. The parents could go under genetic counseling if they believe they will pass on the gene for Pfeiffer Syndrome.
 * Surgical reconstruction over several stages
 * Early surgery to release premature sutures of the skull (usually done in the first year of life)
 * Hearing tests performed early to determine whether or not ear surgery should be performed ([|9]) (A Publication, n.d.)
 * Dentist consultation during second year of life
 * Surgery to enlarge eye sockets
 * Hand surgery to release webbing between fingers

__**Interesting Facts:**__ >
 * 1) Chromosome 8 is the least mapped chromosome for its size.10 (Ridley,1999, p.124)
 * 2) Chromosome 8 has 110 pseudogenes.([|2]) (Chromosome 8(human), n.d.)
 * 3) 8% of the genes found on chromosome 8 are involved in brain development and function.([|2]) (Chromosome 8(human), n.d.)
 * 4) 16% of its genes are involved in cancer. ([|2]) (Chromosome 8(human), n.d.)
 * 5) The short arm of Chromosome 8 has about 45 million base pairs. ([|2]) (Chromosome 8(human), n.d.)
 * 6) The short arm, 8p, has a big region of about 15 megabases that appear to have a high mutation rate, which shows a huge divergence between human and chimpanzee, suggesting that its high mutation rates have contributed to the evolution of the human brain. ([|2]) (Chromosome 8(human), n.d.)

__**References:**__
 * 1) Chromosome 8 - Genetics Home Reference. (n.d.). //Genetics Home Reference - Your guide to understanding genetic conditions //. Retrieved May 13, 2012, from http://ghr.nlm.nih.gov/chromosome/8
 * 2) Chromosome 8 (human) - Wikipedia, the free encyclopedia. (n.d.). //Wikipedia, the free encyclopedia //. Retrieved May 13, 2012, from http://en.wikipedia.org/wiki/Chromosome
 * 3) The Werner syndrome protein: linking the r... [Aging (Albany NY). 2011] - PubMed - NCBI. (n.d.). //National Center for Biotechnology Information //. Retrieved May 13, 2012, from http://www.ncbi.nlm.nih.gov/pubmed/21
 * 4) ANK1 - ankyrin 1, erythrocytic - Genetics Home Reference. (n.d.). //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Genetics Home Reference - Your guide to understanding genetic conditions //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">. Retrieved May 13, 2012, from http://ghr.nlm.nih.gov/gene/ANK1
 * 5) <span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">WRN - Werner syndrome, RecQ helicase-like - Genetics Home Reference. (n.d.). //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Genetics Home Reference - Your guide to understanding genetic conditions //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">. Retrieved May 13, 2012, from http://ghr.nlm.nih.gov/gene/WRN
 * 6) <span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;"> DNA Helicase. //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Advanced Computing Lab at St. Edward's University //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">. the. (n.d.).Retrieved May 13, 2012, from http://www.cs.stedwards.edu/chem/Chem
 * 7) <span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">The role of DNA exonucleases in protecting genom... [Age (Dordr). 2011] - PubMed - NCBI. (n.d.). //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">National Center for Biotechnology Information //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">. Retrieved May 13, 2012, from http://www.ncbi.nlm.nih.gov/pubmed/21948
 * 8) <span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Pfeiffer syndrome - Genetics Home Reference. (n.d.). //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Genetics Home Reference - Your guide to understanding genetic conditions //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">. Retrieved May 13, 2012, from http://ghr.nlm.nih.gov/condition/pfeiffer-syndrome
 * 9) <span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">A Publication of Children's Craniofacial Assosciation. (n.d.). //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">A Guide to Understanding Pfeiffer Syndrome //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">. Retrieved May 3, 2012, from www.ccakids.com/Syndrome/pfeiffer.pdf
 * 10) <span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Ridley, M. (1999). Self-Interest. //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;">Genome //<span style="background-color: #efefef; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 11px;"> (pp. 123-135). New York City: Harper Collins.