Epidemic Influences

Epidemic Influences
Epidemic has become the term of choice when discussing obesity in North America, and the
struggle against the disease continues since effective long–term treatment has yet to appear. Obese
individuals also often face prejudice, due to a common misperception that their condition solely
results from lifestyle choices. However, studies show that environment accounts only for 50–65% of
occurrence (Campfield et al. 1997, Bouchard and Perusse 1993 as cited by Campfield et al. 1996),
leaving much to genetic influence. Recently much attention has been directed at the OB protein, or
leptin, pathway due to its apparent influence on obesity–related components. Under the current
context, leptin's most important biological role is as an indicator of appetite satiety (Campfield et al.
1996). Generally, leptin levels have been found to increase with food intake and decrease with
hunger (Coll et al. 2007). In normal function, leptin circulates in the bloodstream, and appropriately,
OB–R receptors have been found in the brain and peripheral tissues (Campfield et al. 1996). ...
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A., Smith, F. J., and Burn, P. The ob protein (leptin) pathway – A link between adipose tissue and
central neural networks. Horm. Metab. Res. 28(12), 619–632 (1996). Coll, A. P., Farooqi, I. S., and
O'Rahilly, S. The hormonal control of food intake. Cell. 129(2), 251–262 (2007). Snustad, D. P. and
Simmons, M. J. Principles of genetics 6th Ed. (John Wiley & Sons, Inc., New York, 2012).
Strosberg, A. D. and Issad, T. The involvement of leptin in humans revealed by mutations in leptin
and leptin receptor genes. Trends Pharmacol. Sci. 6(1), 227–230
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Genetic Vs Germline Mutation
Mutation can occurs or take place in several different way which sometimes lead a drastic change,
either for good or bad. Genetic mutation is a permanent change in the sequence of DNA that makeup
gene mutation of these sorts can be caused by either inheritance from parents or caused sometimes
during someone's life long. The mutation that has can be inherited is called a germline mutation.
Germline mutation affects virtually the entire body and they seem to be present in every cell. In
contrast to Germline mutation, a somatic mutation in the DNA of a single cell happen at some point
during someone's life can be cause by the environmental factor or a wrong bonding of molecules.
These cannot pass down to the next generation of children because ... Show more content on
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It results in a cleft palate, heart defects, autoimmune disorders, and more. The symptoms vary wildly
and can be accompanied by learning disabilities and mental illness and are usually shown in
children by the age of two to three based on James B analysis also this happened to 1 out 2500

Dominant Pathogenic Disease Research Paper
) Introduction. What is a dominant pathogenic mutation? Is the KID syndrome a dominant
pathogenic disease? Explain.
A. Dominant pathogenic mutations display their traits despite another copy remains present. The
lethal form of keratitis–ichthyosis–deafness (KID) syndrome is caused by the reversion of the GJB2
nonsense mutation p.Tyr136X that would otherwise have confined the effect of another dominant
lethal mutation, p.Gly45Glu, in the same allele
2) Introduction. What are the symptoms of the KID syndrome? What is the specific mutation that
causes the symptoms? Explain.
A. The symptoms of KID syndrome are vascularizing keratitis, ichthyosiform erythroderma and
sensorineural hearing loss. KID syndrome is mainly caused by a heterozygous germ line missense
mutation in GJB2 encoding Cx26.
3 Introduction. What is the main hypothesis of the paper? Explain.
A. p.Tyr136X mutation is able to confine the pathogenic effect of p.Gly45Glu in the mother and the
reversion of p.Tyr136X ... Show more content on Helpwriting.net ...
The blood cells of the patient did not show mosaicism, and the patient's skin symptoms were fairly
evenly distributed over the entire body surface. These findings suggest that the patient was not
mosaic for the GJB2 mutation.
7) Results. What is the role of Gly45 in the Cx26 gene? What is the role of the protein? What does
the p.Gly45Glu do to the protein function? How does the second mutation prevent the disease?
Explain.
A. Connexons containing p.Gly45Glu mutants function as hemichannels with aberrantly increased
activity that leads to the disease manifestations. Gly45 locates at a domain that lines the channel
pore and probably mediates voltage sensing. Cx26 carrying p.Gly45Glu/p.Tyr136X alteration would
be excluded from the hexameric connexons, a second–site mutation cancels an exsisting pathogenic
mutation.
8) Results. What tools did they use to show the localization of the different proteins? What did they
find on the localization and function of the different proteins?

Uner Tan Syndrome Essay
In 2005, a Turkish neuroscientist and evolutionary biologist named Dr. Uner Tan discovered a
family with a very unique condition: five of them walk on all fours with a quadrupedal gait. In
addition to quadrupedalism, affected individuals showed severe mental retardation and what he
described as "primitive speech." The presence of these three characteristic symptoms became known
as Uner Tan Syndrome. The Ulas family was discovered in a small village near Iskenderun in
southern Turkey. At the time of their identification, there were 12 normal children and 7 disabled
children, one of whom died. Of the 6 remaining affected children, 5 of them displayed habitual
quadrupedal walking. The Ulas family is highly consanguineous (second ... Show more content on
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Humans, due to a highly developed cerebellum, have an unparalleled sense of balance that is
specially adapted to bipedalism. MRI scans of all members of the Ulas family showed that the
individuals with Uner Tan Syndrome had grossly underdeveloped cerebellar vermis, which is
responsible for balance and locomotion (See figure 1).
Since the discovery of the Ulas family, three additional consanguineous families in Turkey have
shown segregation for Uner Tan Syndrome to varying degrees. All together, these families were
labeled A, B, C, and D. Families A and D had regular access to medical attention, and both sought
treatment for the quadrupedal locomotion. In fact, family A actively discouraged quadrupedal
walking. Attempts in both families were unsuccessful, which led researchers to conclude that social
factors did not contribute to this behavior (Ozcelik et al. 4234).
Although Uner Tan Syndrome is described as a collection of symptoms, the implications of the
quadrupedal locomotion has caused it to receive the greatest amount of attention since its discovery.
In 2008, Turkish scientists claimed to have found one of the genes responsible, at least in part, to
this particular phenotype. Affected individuals in families A and D were homozygous for either
deletions or nonsense mutations in the VLDLR gene on chromosome 9. This gene transcribes a very
low–density

Unit Title: Biochemistry Of Nucleic Acids.(A.C. 5.1 And
Unit Title: Biochemistry of Nucleic Acids (A.C. 5.1 and 5.2)
The human body is made up of trillions of cells and each cell has a nucleus, filled inside with
chromosomes made of a long string of DNA (deoxyribonucleic acid) wrapped around a special
protein called histone (American cancer society 2014). According to Cancer Research UK (2014)
DNA by itself is made up of thousands of genes, which are a coded message that tell the cell how to
behave and divide. As such if the signals are missing, cells replicate excessively and mutate,
forming a tumour, and later, a primary cancer (American cancer society 2014). Figure 1.1. Mutation
of the DNA leads to severe diseases such as cancer. (Midhath ... Show more content on
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In contrast missense mutation is where one DNA nucleotide is switched out with another one in a
way that changes the amino acid specified. Whereas in silent mutation, there is no any change in the
amino acid sequence of the protein product (Study 2017). Figure 1.2. Types of mutations. (Study
2017).
Moreover, it's important to understand that gene mutation occurs in our cell all the time.
Accordingly, the prevention of cancer is profoundly dependent on the p53 tumour suppressor
protein, which is the process to eliminate excess, damaged or infected cells by apoptosis (Haupt
2003). But if the cell doesn't die in the process of apoptosis, it may lead a person to developing a
cancer. Oncogene are a sequence of deoxyribonucleic acid (DNA) that has been altered or mutated
from its original form and induces cancer (Encyclopaedia Britannica 2017). Some people have high
risk of developing cancer because they inherited mutations in certain genes (Cancer research UK
2014). Mutation are classified into two, inherited and acquired types of mutation, widely discussed
below (ASCO 2017)
Acquired mutation is not present in human reproductive system, but is acquired sometime later in
life which are commonly known as sporadic (somatic) kind of mutation (American cancer society
2014). This type of mutation causes

Idiopathic Congenital Nystagmus : A Disease Characterized...
INTRODUCTION. Idiopathic congenital nystagmus, or idiopathic infantile nystagmus is a disease
characterized by the rapid, involuntary eye movement. This movement is typically in the horizontal
direction, however, movement in other directions have been observed. One way to get nystagmus is
through genetic mutations. Nystagmus caused by genetic mutation is seen at a relatively young age
but cannot yet be treated. The disease is not understood well, it is believed that the cause is a
developmental defect. The linkage, and inheritance has not been identified, the patterns suggest that
multiple genes are involved in the disease and that there are loci on different chromosomes with
three of the five loci located on the X chromosome. Mutations have been linked to the FRMD7
gene, a gene that consists of 12 exons, of the FERM family. The function of FRMD7 have yet to be
determined however an abundance of the protein in the brain in areas associated with the eye.
Mutations within this region consist of missense, deletion, tranversion and nonsense mutations.
Over forty–four mutations that lead to ICN have been found in the FRMD7 gene. Learning more
about the mutation of FRMD7 in ICN is important because these mutations may prevent elongation
of neurite processes during diﬀerentiation preventing axons from responding to stimuli (Watkins et
al. 2012). INHERITANCE. Idiopathic congenital nystagmus can be inherited, however the
inheritance pattern is debatable and penetrance varies among

LOX Syndrome
How was the LOX mutation found in TAAD?
LOX is the major cross–linking enzyme in the extracellular matrix of blood vessels, and loss of its
activity results in blood vessel dilation and rupture. Even though there is no known human disease
associated with an alteration in the LOX gene, a variety of genetic disorders had been linked to this
mutation. Examples of these are Menkes disease, occipital horn syndrome, Thoracic Aortic
Aneurysm and Dissection (TAAD), among others. The LOX mutation was discovered by using
whole–genome sequencing in a family exhibiting autosomal dominant TAAD. Two individuals from
this family affected with TAAD were analyzed, and researchers were able to identify a missense
mutation in the lysyl oxidase (LOX) gene, ... Show more content on Helpwriting.net ...
With the use of autofluorescence, researchers were able to identify the majority of the breakage
throughout the aorta, which suggests that M298R mutation causes loss of function of the LOX
enzyme. Even though heterozygous mutant mice had no manifestation of a disease, the increased in
length of their ascending aorta and the fragmented elastic fibers suggest that mutant animals may be
predisposed to vascular diseases. These findings may help explain why not all individuals in the
family develop aneurism and are only affected with arterial torsion.
4) What is the phenotype of mice having homozygous LOX gene mutation?
Mice homozygous for the mutation in LOX gene were normal in body size compared to mice
heterozygote for the mutation, however, hemorrhages cause by internal bleeding were frequently
detected, as well as severe kyphosis and ruptured diaphragms. The finding of blood clots around
blood vessels indicate that aneurysmal rupture was frequent in homozygous mice. These animals
were born within the expected phenotypic ratio but died a few hours of birth due to ruptured

C-Terminal Globular Domain Of Gene Case Study
Sabrina Anikina
1.i gene product: C–Terminal Globular Domain of human lamin A/C species: Homo Sapien ii
homolog gene: LMNA species: Mus musculus iii ncbi identification number: NP_001002011.2 iv
omim identification number: 150330 v genetic disease: Emery–Dreifuss Muscular Dystrophy 3
phenotype mim numbers: 616516
2. The human gene has 17 exons and the homolog has 15 exons, but both are located on
chromosome 1. The concentration of the transcript is highest in the colon of the homolog and in the
gall bladder of the human. The homolog produces 3 different isoforms of the protein with all three
having the same function of either being a domain in the lamin tail (responsible for the hydrolyses
of other proteins like ... Show more content on Helpwriting.net ...
The study was completed using a yeast cells that were exposed to UV radiation at the G1 stage. The
cells that were exposed before the G1 phase showed almost no delay time during the checkpoint
stage to S phase, but cells that were only treated with radiation after the G1 stage showed a longer
delay time for budding. This study determined that the cells initially exposed to radiation had the
DNA damage checkpoint severely affected by the exposure. The same was done for the G2 phase.
https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=286837
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC305794/
4. The mutation, inherited in the autosomal dominant fashion, causes a change in the mRNA (3' end)
of the lamin a/c proteins. This will produce a dominant negative effect of the proteins to change the
conformation of the nuclear envelope and lamina during interphase by changing the placement of
the emerin protein (that has an interaction with the lamin a/c proteins in the nuclear lamina) and the
SUN1 protein. This primarily affects neurons in a way that they cannot move the nucleus into
clusters where there is a junction of nerves, altering the neuromuscular junction. The wrong position
of the nucleus didn't allow for the neuronal signal to be transmitted through the neurons, and in turn
the muscles couldn't change their conformation.

##otype-Phenotype Correlation Prediction By In Silico...
3.1 Genotype–phenotype correlation prediction by in silico approaches
To solve Q1 and Q3 in Figure 1, we evaluated the performance of each tool in a variety of genes
associated with lysosomal diseases. To evaluate the false negative rate of each tool, we submitted all
385 known disease–associated missense mutations of IDUA, IDS and GLB1 genes into these tools.
Significant concordance was observed between the functional consequences of missense mutations
predicted by various combinations of the tools. Out of 385 known disease–causing mutations, 155
(40.3%) were predicted to be 'damaging' by all 7 tools and 197 (51.2%) were predicted to be
'damaging' by at least 6 tools. As shown in Figure 2, PROVEAN and PolyPhen turned out to be the
most ... Show more content on Helpwriting.net ...
3.2 SAAMP algorithm 2.0 Due to the inherent false positives and negatives associated with each
tool, combing different tools is expected to remarkably increase the accuracy. In our previous study
[6], by integrating outcomes of these 7 tools (SIFT, PolyPhen, PROVEAN, PHD–SNP, PANTHER,
SNPs&GO and I–Mutant), a SAAMP algorithm with a pathogenic index (PI) was developed. PI is
defined as percentage of 'damaging' predictions from these 7 tools (ranging from 0 to 1), where the
higher the PI is, the more pathogenic the mutation is. The cut–off value was set at 0.43. When PI
was ≥ 0.43 (larger than or equal to 3 'damaging' predictions), the mutation was defined as
'pathogenic', otherwise 'benign'. When tested in the IDUA gene, a sensitivity of 93.8% and a
specificity of 80% was achieved, which was better than any individual tool. In this study, by testing
each tool in a broad array of genes (Figure 2), we determined the widely varying performances of
these tools. Therefore, we decided to optimize the SAAMP algorithm by excluding PANTHER,
SNPs&GO and I–Mutant based on their modest performances. SAAMP 2.0 only included
PROVEAN, PHD–SNP, SIFT and PolyPhen, and defined the cut–off value of PI as 0.5 (larger than
or equal to 2 'damaging' predictions). Notably, there was no specific order for using these 4
bioinformatics tools. Since the performances of the remaining four tools were quite similar, we
treated each tool

Genetic And Epigenetic Influences On Autism Spectrum...
Genetic and epigenetic influences in autism spectrum disorders: A role for the methyl
CpG–binding protein in Rett syndrome.
The genetics of neurodevelopmental disorders (NDD) rarely display a Mendelian mode of
inheritance, and can result from a single rare gene mutation, more common variations in single
nucleotide polymorphisms, or often a combination of these two factors in conjunction with
environmental influences [1]. In contrast, epigenetic mechanisms are heritable changes in gene
expression which do not change the DNA sequence [1]. Epigenetic changes to the genome may
predispose the development of NDD when combined with the aforementioned genetic risk factors
[1].
Autism Spectrum Disorders
Autism spectrum disorders (ASD) are a class of NDD affecting mostly males, which are largely
idiopathic and display extensive variation in terms of phenotype, severity and degree of heritability
[2]. It is postulated that the pathology of ASD is the result of a complex interaction between genetic
predisposition and environmental risk factors, which disturb the developing brain [1]. ASD
commonly involve deficits in social interaction and cognition, language, emotional learning and the
presence of repetitive, stereotyped behaviours [1, 3, 4]. The brains of autistic children display
reductions in long distance connectivity, abnormally regulated apoptosis and cell division, and
increased inflammation [4].Additional studies have demonstrated gliosis, abnormal neuronal
migration and

Witkop Syndrome Essay
Witkop syndrome is manifested by defects in the nail plates of fingers and toes typically and
hypodontia, with normal hair and sweat gland function. There is a pattern of missing teeth.8 Absent
maxillary incisors, second molars, and maxillary canines are the most common missing teeth.9
Genetically, mutations in genes MSX–1, PAX9, PsITX2, LTBP3, WNT10A, EDA and EDARADD,
AXIN2, and IKBKG have been found associated with oligodontia. Mutations in MSX–1 have been
shown to be associated with Witkop's syndrome.[10)
Cosegregation of the phenotype with a heterozygous stop mutation in the homeodomain has been
revealed through direct sequencing and restriction–enzyme analysis. In a study histological analysis
of Msx1–knockout mice, combining a finding of Msx1 expression in mesenchyme of developing
nail beds, revealed that both tooth development as well as nail development were disrupted. A
nonsense mutation in MSX1 causes TNS and Msx1 is critical for both tooth and nail development as
both develop via epithelial–mesenchymal ... Show more content on Helpwriting.net ...
They have shown that there is complete cosegregation between the 605(C→A) nucleotide
substitution and people affected by this syndrome. Located in the homeobox coding region in exon
2, the aftermath of this mutation was a stop codon at amino acid position 37 of the homeodomain.
The conjectural lost part of the protein was known to be significant for protein stability (helix II)
(Hu et al. 1998) and DNA binding (helix III) (Isaac et al. 1995). The abbreviated protein thus
formed lacked in part of the homeodomain and the entire C–terminal region was unable to bind to
DNA causing the dominant phenotype of Witkop syndrome through haploinsufficiency, instead of a
dominant–negative mechanism. This was also substantiated by a study where a missense mutation
(R196P) in the homeodomain of MSX1 causes familial tooth agenesis

Achondroplasia Essay
Achondroplasia (ACH) is the most common form of short–limb dwarfism occuring in 1 in 15,000 to
28,000 births and appears to be slightly more prevalent in females, but indiscriminent toward race
(1–3). Evidence has been found in Egypt for cases of ACH dating back as far as 4500 B.C. (4). In
simplest terms, ACH is a disease where the dwarfing of bones formed in the cartilage occurs (5).
There are many features that accompany this disease including rhizomelic (proximal) shortening of
the extremities, megalencephaly (enlarged brain), short stature, trident hand, and frontal bossing
(prominent forehead) (1, 3, 4, 6–8). Expression of this gene at high levels is primarily found in cells
of the nervous system and the cartilage rudiments and ... Show more content on Helpwriting.net ...
A point mutation is one where only one nucleotide is changed and a missense mutation is when the
amino acid changes due to the base(s) mutated. FGFR3 consists of 19 exons, with the mutation
occuring in exon 10 (1, 16). Furthermore, the mutated base is 1138, where the base can undergo two
possible mutations. G(guanine)→A(adenine) transition accounts for 98% of all cases of ACH while
the G→C(cytosine) transversion mutation occurs in 1% of cases (6). Both of these mutations result
in the amino acid arginine being substituted for glycine at codon 380 which is in the transmembrane
of FGFR3 (1, 4, 17) (See Figure 1). The FGFR3 mutation is a gain–of function mutation due to the
resulting activation of receptors, which is opposite the normal inhibitory effect the FGFR3 has on
the receptors, which upon activation, negatively regulate bone growth (4, 6). Thus, FGFR3 has been
found to become hyperactivated when mutated and undergo ligand–independent dimerization (1, 11,
18). De novo mutations account for 80–90% of all cases of ACH (1, 4, 7, 8, 11). Recent research has
determined that increased paternal age correlates to this specific mutation occuring (4, 7, 11, 19).
The maternal age seems to have no effect, meaning that the de novo mutation occurs during
spermatogenesis (20). This has also been studied and each affected individual was found to have
received the mutated chromosome paternally (21). There has only been one documented case of an

Essay On Mutation
Spontaneous mutations occur during a normal cell process creating genetic changes (text p.206).
There are varying types of spontaneous mutations including, silent, missense, nonsense, and
frameshift mutations. How are these mutations the same and how are they different? Silent,
missense, and nonsense mutations all occur when base substitutions happen (text p.206). A base
substitution is when the wrong nucleotide is incorporated during DNA synthesis, this is the most
common mutation (lecture). In a silent mutation a base substitution occurs, incorporating an
incorrect nucleotide, the result is a codon that codes for an amino acid that is the same as the wild
type (text p. 206). In a missense mutation, the resulting mutant codon does not ... Show more
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These mutations are ones that often produce stop codons, putting a halt to the creation of the protein
with shortened amino acid sequences. They may also generate proteins that do not function. By
simply adding a single nucleotide you alter the coding outcomes of the remaining nucleotides down
the sequence. If one were to insert a sequence of three nucleotides, they would be inserting a
complete amino acid. Because of this, there is a higher likelihood that the sequence of three
nucleotides would simple produce a new amino acid, rather than a stop codon, unless it itself was a
stop codon. This creation of a new amino acid to the sequence would elongating the genetic
sequence and continue to produce a functioning protein while allowing the remaining gene sequence
to remain the same. Example 1.1: Insertion into a reading frame:
Reading Frame 1: Wild Type
AUG–––UUA–––UCA–––UAU–––AUC–––UAG
Met Leu Ser Tyr Ile STOP
The above frame demonstrates gene sequence with start and stop codons.
Reading Frame 2: Single Insertion:
AUG–––UUA–––UCA–––UAA–––UAU–––CUA–––G
Met Leu Ser STOP Tyr Leu The above frame demonstrates gene sequence with the insertion of a
single nucleotide, resulting in a stop codon.
Reading Frame 3: 3 Nucleotide Insertion:

AUG–––UUA–––UCA–––CCU–––UAU–––AUC–––UAG
Met Leu Ser Pro Tyr Ile Stop
The above frame

Essay On Polymorphisms
Using the whole genome sequence results of 9 cats, non–synonymous single nucleotide
polymorphisms (SNPs) in P2RY1, P2RY12, and CYP2C19 genes were identified (Table 2). Among
these SNPs, the p. P479L missense mutation in CYP2C19 gene on cat chromosome D3.56761959
caused by a cytosine–to–guanine (C>G) transversion has a high probability of altering protein
morphology and/or function predicted by PolyPhen2 with a damaging score of 0.997 (sensitivity:
0.41, specificity: 0.98). In addition, the p.A236G missense mutation in P2RY1 gene on cat
chromosome D2.110685284 caused by a guanine–to–cytosine (G>C) transversion had some
probability to cause functional modification of the P2Y1 ADP receptor predicted by PolyPhen2 with
a damaging score of 0.256 ... Show more content on Helpwriting.net ...
In humans, patients with the CYP2C19 variant are often classified as decreased responders to
clopidogrel and shows higher platelet activity and aggregation resulting in the higher risk of
developing thromboembolic events such as coronary artery infarction and stroke (Simon T et al.
NEJM 2009, Mega JL et al. Lancet 2010). In addition, one study has reported mutations in the
CYP2C19 gene as the key gene variant that influences the reactivity and pharmacodynamics of
clopidogrel in patients causing clopidogrel resistance (Price MJ et al. J Am Coll Cardiol 2012). In
the present study, cats with HCM frequently possess the p.P479L missense mutation in the
CYP2C19 gene which is predicted to cause low or no–response to clopidogrel therapy in cats. In
addition, the p.A236G mutation in the P2RY1 gene had some probability to cause function
modification of the P2Y1 ADP receptor, and each of the identified polymorphisms are seen in highly
conserved amino acids (Table 3). In human patients with cardiovascular disease, carriers of
mutations in P2Y12 gene had an increased risk for developing thromboembolic diseases (Ziegler S
et al. Stroke 2005). Although the p.V34I missense mutation in the P2RY12 gene was predicted to be
benign, it is still reasonable to further investigate this mutation in response to the effect on platelet
activity with clopdigorel administration in cats. Hypertrophic cardiomyopathy (HCM) is one of the
most common inherited cardiac disease in humans and

Hereditary Spastic Paraplegia Lab Report
Hereditary spastic paraplegia (HSP) is a heterogeneous class of diseases marked by lower limb
weakness and spasticity due to progressive degeneration of axons in the corticospinal tract. HSP has
been linked to mutations in the neuronal motor protein, kinesin Kif5A. The function of this protein
is to transport cellular cargo from cell bodies to synaptic terminals. We hypothesize that the disease
is caused by ineffective transport of cellular cargo. Fifty percent of the known disease–causing
mutations are in the region of Kif5A that interacts with microtubules. We have previously shown
that disease–causing missense mutations in the motor domain of Kif5A cause a reduction in kinesin
motility rate, as well as reduced microtubule binding affinity. ... Show more content on
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To mutagenize human Kif5A (WT), we performed PCR–mediated site–directed mutagenesis to
insert our mutation into the plasmid vector (shown to the right). Next, we performed a restriction
enzyme digest with Dpn1, to digest the parental plasmid. The presence of the PCR product was
confirmed by performing gel electrophoresis where the expected band of 6.8 kilobases was
obtained. The remaining DNA was used in a bacterial transformation of DH5α to grow colonies.
Liquid cultures were grown from overnight colonies and Minipreps were performed to purify the
plasmid DNA. These plasmids were sent for sequencing, where the P278L mutation was confirmed.
Figure 3. Protein expression and purification protocol is shown in the schematic in (A). To confirm
expression of the P278L mutant, a western blot was performed. Note the presence of Kif5A in all
fractions, and enriched in the E1 and E2 eluate.
Figure 4. We created a flow chamber in which kinesin was nonspecifically bound to a coverslip. As
shown in (A), fluorescently–labeled microtubules were flowed in and the kinesin transported the
microtubules. A sample timelapse set of images is shown in (B). None of the mutants were able to
bind microtubules at our standard assay condition salt concentration of 50 mM NaCl. At lower salt
concentrations, most L11 and L12 mutants had decreased velocities when compared to wildtype.
However, P278L exhibited "rigor binding", meaning kinesin was bound to microtubules, but there
was no

DNA Translocation
A DNA translocation occurs when chromosomes that do not contain the same genetic information,
also known as nonhomologous chromosomes, rearrange and fuse portions of their chromosomes to
one another. This results in a portion of a chromosome and possibly genes becoming a part of a
chromosome they are not traditionally found on, resulting in defective, partially functional, or
nonfunctional genes and chromosomes. Julia has acute promyelocytic leukemia; the high amount of
immature blood cells, anemia, and thrombocytopenia are all crucial indicators of this type of cancer.
The fatigue, formation of frequent bruises, and non–painful lumps are all symptoms of this cancer as
well, since the leukemia affects the blood cells; the reduced number of ... Show more content on
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The specific gene that RARa suppresses is those involved with the differentiation of white blood
cells past their promyelocyte phase.
In the mutated hybrid version of these two genes, they still act as gene repressors, and bind the
sections of the DNA related to white blood cell proliferation. Instead of responding to signals that
would normally cause RARa or PML to dissociate, the gene repressor remains on the DNA,
effectively almost always blocking transcription of the gene. Since the proteins involved in assisting
a white blood cell differentiate past the promyelocyte phase are rarely, if ever, transcribed, new
white blood cells remain in this unmatured stage and cannot complete their differentiation into fully
functioning leukocytes. In addition, the PML protein also loses other functions, such as inducing
apoptosis and preventing uncontrolled cell proliferation. Because of this, cells that should begin
apoptosis remain alive, and cell proliferation is not regulated, allowing uncontrolled growth. As a
result of the cumulation of protein function abnormalities, PML–RARa blocks promyelocyte stage
differentiation, and allows excess promyelocytes to proliferate. These immature cells then go on to
accumulate in the bone marrow and joints, leading to pain and possible metastasis as they travel
through the bloodstream.
Other Genes Involved in Acute Promyelocytic Leukemia FLT3 is another gene involved in the onset
of promyelocytic leukemia, and produces fms–like

Superoxide Dismutase 1 : The Causes And Consequences Of SOD1
Superoxide dismutase 1 is the most commonly ALS aggregated protein to be identified since its
discovery over two decades ago (Rosen et al., 1993; Tortelli et al., 2013). SOD1 is a 153 amino acid
homodimer with a copper–zinc active site (Brotherton et al., 2013; Dangoumau et al., 2014). Mutant
SOD1 is responsible for the loss of motor neurons and constitutes an estimated 20% of the familial
ALS (fALS) cases (Brotherton et al., 2013; Tortelli et al., 2013). Wild type SOD1 is universally
expressed in all cells and is responsible for the removal of free radicals often in the form of reactive
oxygen species (ROS) (Brotherton et al., 2013; Chiang et al., 2017). Damage to DNA and
degradation to metabolic processes occur due to accumulation of ROS ... Show more content on
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Soluble misfolded proteins are generally regulated by autophagy while insoluble misfolded proteins
are primarily targeted by ubiquitination and removed by proteasomes. TDP–43 and SOD1
aggregates form insoluble clusters in the cytoplasm (Keskin et al., 2016; Neumann et al., 2006;
Parakh et al., 2016; Pickles et al., 2016; Pokrishevsky et al., 2012). Conversely, studies have shown
that wild type SOD1 is less soluble than the misfolded SOD1, and the more soluble the misfolded
protein is from the mutation, the more toxic the misfolded SOD1 becomes for the cell (Brotherton et
al., 2013; Xu et al., 2014). Furthermore, soluble misfolded SOD1 has a significant affinity for the
mutant SOD1 variants, which may present a mechanism for increased toxicity in sporadic ALS
patients (Xu et al., 2014). This suggests that soluble misfolded SOD1 associates with SOD1
aggregates, and could cause further mislocalization and accumulation of mutant SOD1. Surprisingly,
when mutant SOD1 was co–expressed with wild–type SOD1 it become more toxic, suggesting that
the wild–type SOD1 enhanced the toxicity of the mutant SOD1 (Brotherton et al., 2013). Mutant
SOD1 variants were placed in lysates of fibroblasts with inhibited proteasome and autophagy. The
misfolded SOD1 proteins greatly increased toxicity with the proteasome inhibited (Brotherton et al.,
2013; Keskin et al., 2016), while the opposite was true for the autophagy inhibited fibroblasts
(Keskin et al., 2016). This suggests protein digestion of

Mutations In The MSX1 Case Study
Mutations in the MSX1 gene cause a variety of diseases. Mutations hit different sites on msx1 that
resulted in different phenotypes. It has been identified some mutations' locations such as in frame
mutations, including 18 missense mutations and truncating mutations, including 5 nonsense
mutations, 5 indel mutations, 1 splice variant, 1 nonstop variant, and 1 entire gene deletion. Farther,
some of these mutations disturb the homeodomain and some don't but located in N terminus protein.
The indel mutations and the missense mutations severely disturb the DNA binding domain (4).
These mutations in homeodomain are associated with tooth agenesis with or without orofacial
clefting. The outside homeodomain mutations are associated with ... Show more content on
Helpwriting.net ...
Another type is oligodontia, which is six or more, represented by 0.1%. They analyzed three
generations of tooth agenesis Japanese family by using whole exome sequencing (WES). They
found that a novel single nucleotide substitution in the MSX1 intron which makes splicing occurs at
7bp instead of the normal splicing site which is the exon 2, resulting a "C–terminal truncated gene
product". This substitution is inserted between the positions 451 and 452. It is worth notice that
insertion is (3).
Another study conducted in Japan family with non–syndromic tooth agenesis. The authors identified
a novel frameshift mutation by using mice with CRISPR/Cas system. The mutation occurred in a
highly conserved C–terminal domain of MSX1, (MH6). Homozygous mice at E16.5 showed
agenesis of lower incisors with or without cleft palate. 4–week–old mutant mice showed agenesis of
the upper third molars and the lower second and third molars. Besides, the upper second molars
were small (12). Furthermore, a study involved six Japanese families with non–syndromic tooth
agenesis. There was a novel nonsense mutation in exon 1 in a family with oligodontia. This
mutation made a termination codon in the first exon, which led to truncated W139X at the C
terminus and no homeodomain MH4. Missing MH4 resulted in losing DNA binding, protein–protein
interaction, and nuclear localization

What Is The Inactivation Mechanism Of Tumor Suppressor Genes?
Inactivation Mechanism of Tumor Suppressor Genes
Tumor suppressor genes encode proteins, inhibiting excessive cell proliferation and division,
through protein inhibitors for cell cycle progression or promoting differentiation and apoptosis via
proteins that involved in induction of apoptosis. Mutations that cause inactivation or loss of function
in these tumor suppressor genes, result in inactivation of P53, pRb, PTEN, NF1/NF2. The mutations
can be deletion or insertion, nonsense or missense mutations, frame shift mutations, or epigenetic
tuning events such as methylation, which lead to neoplasia. These mutations are recessive and
clinically important, only when they appear as homozygous or a combination with heterozygous
alteration. The ... Show more content on Helpwriting.net ...
Although, following the first allele alteration, the cell genotype will not change, but it may increase
the rate of cell proliferation, prompt to trigger cancer in the cell. Then, the second mutation, causing
inactivation of the second allele is much more likely to happen, compared to than the first mutation .
In recent years, the evidences show that this theory cannot be generalized. Significant evidence
represented that the lack of only one allele in several tumor suppressor such as P53, PTEN, SMAD4
is sufficient to disable the synthesis of the gene product and may promote the tumorigenic process,
called haploinsufficiency. In this case, tumor suppressor genes lead to tumorigenesis, without an
inherited mutation in an allele.
Promoter methylation is a regulatory system for gene expression. In some cases, without any
mutations in tumor suppressor genes, incorrect methylation on several tumor suppressor genes lead
to gene silencing, an increased scale of proteasomal degradation and abnormalities of protein
function.
PTEN
As previously mentioned, phosphate and tensin homolog gene, PTEN is a kind of tumor suppressor,
associated with negative regulation of some pathways such as PI3K signaling pathway. The loss of
PTEN activity has been shown in Cowden's syndrome, seen to increase risk of some cancers,
including breast and thyroid cancer. The mechanism of PTEN

Syndactyly Essay
Type II syndactyly or synpolydactyly(SPD) is a semi dominant inherited limb malformation that
involves a fusion of digits. It is caused by mutations in HOXD13 on chromosome 2 due to
polyalanine repeat expansions. Polyalanine repeats in SPD are mitotically and meiotically stable,
causing polymorphisms to be rare, unlike other nucleotide repeat expansions such as Friedreich's
ataxia. HOXD13 is a member of the HOX family, a family of transcription factors that are proteins
which contain homeodomain that are important for controlling cell fate along the limb axes and
body. HOXD13 is a part of the HOXD gene cluster and crucial for limb development, particularly
during the early and late stages of limb development. The stage occurs during the creation of the
limb buds at week 4, during this stage the limbs have AP polarity through the expression of sonic
hedgehog(shh) signaling from the zone of polarizing ... Show more content on Helpwriting.net ...
The second stage occurs during the outward growth of the distal limb regions which depends greatly
on sonic hedgehog expression at week 6 day 52 is when hand is fully formed. In both stages HOXD
genes are critical since they are involved in initiation of shh expression during the earlier stage and
mediation of shh signaling from within the limbs during the second stage. The resulting phenotype
of HOXD13 mutants display limb malformations. There is much fewer missense and nonsense
mutations in HOXD13 and the most common mutation is the addition of 7–14 in the N–terminal
polyalanine repeats of the HOXD13 gene. When the gene is abnormal from the polyalanine repeat
mutation, it produces an abnormal protein which destabilizes the normal protein confirmation,
causing aggregation. Once this occurs, it halts the protein translocation which occurs from the
cytoplasm to the nucleus where it acts as a transcription factor. Additionally, the size of the
polyalanine repeats directly correlates with the severity of

Genetic Synthesis Essay
The effects that ALS (Amyotrophic Lateral Sclerosis) has on the human body at the cellular level
are trademarks of the disease and can be attributed in a large part to genetic mutations causing these
phenotypes. ALS is autosomal dominant, meaning that if one parent has a gene that causes ALS,
there is a 50% chance that one of their offspring may also have one of the genes that causes ALS.
Men are slightly more likely to get ALS at a younger age than women are at a younger age but this
gap begins to dwindle as the ages of people with ALS increases. Despite the fact that many genes
have been discovered that cause ALS, a large portion of genes and mutations have yet to be found.
The two groups of ALS, familial and sporadic, both have genetics ... Show more content on
Helpwriting.net ...
This mutated FUS protein results from another missense mutation. In order to figure out exactly
where this mutation took place, researchers sequenced 279 exons form 32 genes (Vance et al.,
2009). Once mutations were found in TARDBP, a single base–pair mutation was found in exon 15
of FUS. This mutation resulted in the base pair substitution of arginine to cysteine at position 521
(R521C). This position is locate on the C terminus of FUS and was consistent with all cases
examined by the researchers (Vance et al., 2009). Two more missense mutations where later found
one at the same position as before, 521, and the other at position 514. The mutation at position 521
resulted in arginine to histidine substitution and the mutation at the 514 position on exon 14 resulted
in a substitution of arginine for glycine. There was no mutation on any of the exons from 1– 13.
These mutations were not as common as the R521C mutation but were still prevalent in some of the
cases examined by the researchers (Vance et al.,

The Change Of Hemoglobin Changes Essay
Homework #9
Chapter 11:
1. The change in hemoglobin changes as the change in the oxygen in the environment occurs. Each
globin usually has two polypeptide chains encoded by genes that attract oxygen molecules to
different degrees.
2. The pancreas which has two types of cell clusters. A transcription factor is activated and change
the expression of a gene in a way that stimulates some progenitor cells to divide.
3. Proteomics is an area where gene expression emerges. It identifies and analyzes all the proteins
that made in a cell, organ, or body.
4. The histone protein plays major role in interacting with other chemical groups which expose DNA
and shield some sections.
5. Acetyl plays role can start the transcription. Methyl groups binds to a specific amino acid in a
specific histone type. When the CH3 are added methylation spreads from the tail of one histone to
the adjacent histone. The addition of phosphate is example of epigenetic changes. The addition of
these three groups should be balanced.
6. MicroRNA's can affect the gene expression by preventing their translation onto protein. This
blocking function lead to enabling the cells to adapt to change condition.
7. Because the genes in pieces of exons and introns and alternate splicing make it possible for one
store of information.
8. By using different information in a gene, the proteins can be resulted. These information is called
isoforms where the driving force behind which version of a protein a cell makes is

Hyper-Ige Syndrome
Hyper–IgE syndrome, also known as Job syndrome is a condition where the immune system being
affected. Affected individuals tend to have frequent bouts of pneumonia, which caused by certain
bacteria that infects the lungs and cause inflammation. Inflammatory skin disorder called eczema are
also very common for Hyper–IgE syndrome. It is also affect bones and teeth where affected
individuals will have an abnormal curvature of spine, primary teeth do not fall out at the usual time
during childhood but retained as the adult teeth as they grow up, and reduced bone density. Hyper–
IgE syndrome occurs because of the mutations in STAT3 gene where this gene is important to
provide instructions in making proteins. The mutations were either missense

What Are Mutations?
Mutations are the foundation of evolutionary change, and the primary source of genetic variation.
Mutations are changes in the nucleotide sequence that are permanent and can be passed on from
mother to daughter cells during cell division. Mutations can also be passed from parent to offspring,
which is if they occur in the reproductive cells. If the mutation that creates new genes that are
beneficial, and allows an organism to respond to its environment better, then that new gene will have
a higher probability of being passed on to future generations. The individuals that carry the
beneficial allele will be more likely to survive and reproduce. This is the basis of natural selection,
which allows organisms to produce adaptations in response ... Show more content on
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Chromosomes can cause mutations when they are changed. A mutation that can occur is gene
duplication, this occurs when a chromosome has extra genetic material. Even though these gene
duplications are rare, if they occur over the course of many generations this can lead to the
formation of a gene family, which consists of two or more genes that are similar. An example of a
duplication that causes a change in the phenotype is caused by a duplication on chromosome 17
which causes the disease known as Charcot–Marie–Tooth Disease. Another example of a mutation
involving the chromosome would be the ploidy change, this occurs when the number of
chromosomes an organism has changes. For example it goes from having two sets of chromosomes,
then going to three or more sets of chromosomes. Down–syndrome is an example of the ploidy
change, where the affected human has three sets of chromosome 21. Mobile elements can cause
mutation in a DNA sequence. Mobile elements are strands of DNA floating around the cell that
insert themselves in a functional gene and then disrupt its

Familial Cardiomyopathies ( Fc )
Background: Familial Cardiomyopathies (FC) are a collection of cardiac diseases that vary vastly
genetically, and pathologically (1, 2). Hypertrophic cardiomyopathy (HCM) is the most common
form of FC (2). HCM is diagnosed often with left ventricular hypertrophy without a noticeable
increase in external load and smaller ventricular cavity, but with a preserved ejection fraction (3).
That is, the percent of blood leaving the left ventricle (5) does not change. Other pathologies include
interstitial fibrosis, thickening of the media in intramural arteries, and myocytes disarray greater
than 5%; which is a hallmark of HCM (4). HCM shows variability in its penetrance, from a patient
with no symptoms, to having sudden cardiac death (SCD) ... Show more content on Helpwriting.net
...
As a result, many patients that do not fit standard diagnostic criteria may in fact have this form of
HCM (8). This low diagnostic sensitivity can be a contributing factor to the high mortality rate of
TnT related HCM, making understanding its etiology very important. Mutations in TnT mostly seem
to be associated with changes in calcium sensitivity (10). Three mutations seem to be prevalent,
each having varying affects on calcium sensitivity. The TnT–Arg278Cys (R278C) mutation, not
without some debate (15), has been found to have negligible effects on calcium handling, resulting
in a relatively better prognosis for the patient (11). TnT–Phe110Ile (F110I) and Ile79Asn (I79N)
mutations both show a respective increase in calcium sensitivity (10). Their pathologies differ from
most HCM in that very little fibrosis or hypertrophy is seen (12). This is unique, as most HCM has
associated fibrosis, which results in re–entrant tachycardias and possible fibrillation (13). But with
I79N and associated mutations, re–entrant tachycardias have been observed in the absence of any
fibrosis (14). Both the etiology of these mutations and resulting pathology has been researched
extensively in murine and porcine models (14, 15). The I79N, R278C, and F110I mutations were
first identified and characterized by Watkins et al. (16). Families exhibiting HCM had their DNA
sequenced and, using statistical analyses, polymorphisms were

Genetic Factors Associated With Melanoma
Introduction:
The skin is one of the most important organs of the whole human body. It is the largest organ in the
human body and contains various functions including protecting the body from injury and
preventing fluids from leaving or entering the body (Boer et al. 2016). In animals, the skin has
various functions as well. The skin aids with locomotion in bats and aquatic mammals, help
camouflage the body in chameleons, helps with finding mates for deer with their white tail, and
serves for many other purposes. The skin is composed of three layers in the human body: the
epidermis, dermis, and subcutaneous layer. Melanin is produced from melanocytes in the epidermis
of the skin. Melanin is important for protection from ultra–violet (UV) rays. ... Show more content
on Helpwriting.net ...
The CDKN2A gene is responsible for a majority of melanomal families. The CDKN2A gene is
responsible for 10% of families with two members that have melanoma and is responsible for 30–
40% of families that have three members connected with melanoma. The linkage between the
CDKN2A gene mutation and melanoma was found in 1994. (Aoude et al. 2015). The CDKN2A
gene is located on chromosome 9p21. CDKN2A is used to help create two types of proteins, p16
and p14. Both of these proteins have functions that relate to regulating the cell cycle. They also
function as tumor suppressants in the body. When the p16 and p14 proteins are being produced, they
are transcribed on exons. An exon is a part of the gene that helps to create amino acids through
coding (Exon). The process of transcription involves copying segments of DNA into RNA using
enzymes. p16 and p14 are transcribed on different exons (1α and 1β) and use the same second and
third exon when producing their amino acids. The amino acid created are different between the two
proteins. The mutation of the CDKN2A gene occurs in the 1α exon affects the p16 protein during
the transcription stage. Mutations can also occur in the 1β exon where both the p16 and p14 proteins
would be affected. Affecting one

Missense Mutation Essay
2. Materials and methods
2.1 Dataset
Known disease–associated mutations were retrieved from The Human Gene Mutation Database
(http://www.hgmd.cf.ac.uk/ac/index.php). The benign polymorphisms were retrieved from the NCBI
dbSNP (http://www.ncbi.nlm.nih.gov/snp/) and previous literature. A variety of genes responsible
for different lysosomal diseases were analyzed in this study and listed here. IDUA,
mucopolysaccharidosis type I (MPS I); IDS, MPS II; GLB1, GM1 gangliosidosis or Morquio
disease, type B (MDB); HEXA, Tay–Sachs disease; HEXB, Sandhoff disease; GBA, Gaucher
disease; CTNS, cystinosis; GAA, Pompe disease; GUSB, MPS VII; SGSH, MPS IIIA; LIPA,
lysosomal acid lipase deficiency.
2.2 Predicting Functional Context of Missense Mutation ... Show more content on Helpwriting.net
...
The output is the predicted free energy change (DDG), which classifies the prediction into one of
three classes: 'decrease' (DDG (–– removed HTML ––) 0) [9].
PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org) is a sequence based predictor
that estimates the impact of mutations on protein function [10]. In PROVEAN, BLAST hits with
more than 75% global sequence identity are clustered together, and top 30 such clusters from a
supporting sequence are averaged within and across clusters to generate the final score. A protein
variant is predicted to be 'deleterious' if the final score is below −2.5, otherwise 'neutral'.
PANTHER (http://www.pantherdb.org/) is a database that predicts the occurrence of an amino acid
at a position in a family of evolutionarily related proteins [11]. PANTHER uses hidden Markov
model (HMM) based statistical modeling methods and multiple sequence alignments (MAS) to
perform evolutionary analysis of SNPs. By calculating the substitution position–specific
evolutionary conservation score (subPSEC), PANTHER estimates the likelihood of a particular
amino acid substitutions causing a functional impact. Based on subPSEC scores, PANTHER
classifies mutations as 'deleterious' (score (–– removed HTML ––) −3), with a probability score (0 to
1).
SNPs&GO (Single Nucleotide Polymorphism Database & Gene Ontology;
http://snps.biofold.org/snps–and–go/snps–and–go.html) is a support vector machine (SVM)
classifier that

Evolutionary Theory Of Natural Selection
Evolution in terms of biology is defined as decent with modification and can be explained by the
rise in diversity from generation to generation based on changes in the gene frequency. When
changes occur in an individual's genome, known as mutations, they give the individual different
characteristics that can have a negative, positive, or neutral effect. If the mutation better adapts the
individual to the environment, that mutation can be passed onto a new generation. If the mutation
weakens the individual to the environment, that mutation will not be able to withstand multiple
generations through progeny. This mimics Darwin's theory of natural selection, which states that the
individuals best fit to the environment have a higher survival and reproductive rate. Over time, these
mutations contribute to genetic variation within species (yourgenome).
The basic building block of all living things, cells hold within them the genetic blueprint that drives
all living things: DNA. DNA is made up genes, which are made up of a series of nucleotides:
Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). Through complementary base pairing,
these nucleotides hydrogen bond with each other to create an intertwined double helix. The
organization of these nucleotides determines the genetic code of the organism. Since all cells are
made up of DNA, DNA replicates itself prior to starting both mitosis and meiosis, processes
required for cell proliferation. In these processes, although errors

Correlation Between Type Of Mecp2 Mutation And The Degree...
Once the MEPC2 gene was implicated in RTT there was an intense period of cohort screening in an
attempt to elucidate genotypic–phenotypic associations (Weaving, 2005). As it stands there are an
approximate 800 pathogenetic mutations that are currently found within the MEPC2 (Cheadle,
2000). These include missense, nonsense, frame shifts and inversions as well as large deletions
which have now been identified as being present in 15% of apparently MECP2 mutation negative
individuals. These large deletions would have gone undetected without the application of NGS
techniques (Weaving, 2005). Work by Wolffe aimed to explore the associations between the type of
MECP2 mutation and the degree of phenotypic severity. While work in this area is largely conflicted
his study was concurrent with previous work concerning the view that particular mutations that were
either point mutations, such as p.Arg133Cys, p.Arg294X, p.Arg306Cys and 3' truncations resulted
in a reduction in the severity of symptoms. There is also a wide consensus that missense mutations
produce a less acute phenotype than nonsense mutations and that the most severe clinical features
were the consequence of splice sites or large insertions or deletions (Weaving, 2005). The MEPC2
gene codes a protein, which is apart of the methyl–CpG–binding family. It contains three conserved
functional domains. Work by Wolffe also examined which aspects of the protein were affected by
each type of mutation. He found that Nonsense

4 Forces Of Evolution Research Paper
The four forces of evolution are natural selection, mutation, genetic drift and gene flow. Natural
selection occurs when organisms with better traits reproduce and pass their traits to their children.
Mutations are when genes are altered in the DNA whether it would occur through the deleting,
rearranging or inserting genes. Genetic drift is a random instance that can potentially remove
variation from a population's genes and cause changes in allele frequencies. The two types of
genetic drift are the bottleneck effect, when a population's size decreases drastically and the founder
effect, when a small group from a population move and reproduce in a different location from the
original. Gene flow is when genes exchange between two very different

Symptoms And Treatment Of Hypertrophic Cardiomyopathy Essay
Keywords: HCM, sarcomere, thick and thin filaments, gene mutation, autosomal dominant, Doppler
echocardiography, dual–chamber pacemaker, septal ablation, myomectomy)
Hypertrophic cardiomyopathy, HCM is a cardiac disorder with a genetic etiology, characterized by
hypertrophy of the myocardium It is an important cause of morbidity and mortality in the affected
population. Both men and women are affected equally and people of any age and race are at risk of
developing HCM. It is the most common cause of sudden cardiac death SCD in young adults,
especially athletes.
Description of the disorder Hypertrophic cardiomyopathy is characterized by interventricular septal
hypertrophy (in absence of other cardiovascular conditions), causing decrease of left ventricle cavity
and potentially leading to outflow obstruction. (1) (6) As a consequence of mutations in several
genes encoding for thick and thin filaments which build the cardiac muscle, morphological changes
occur leading to tangled, thickened myocardial fibers. It is an important cause of morbidity and
mortality. Symptomatology varies a lot, from asymptomatic patients to those with severe cardiac
function impairment. Some of the most common symptoms of HCM, which are not specific to this
disorder may be: shortness of breath at rest or with exertion, fatigue, chest pain, arrhythmias,
dizziness, but not only.
There is an ongoing debate about the onset of the hypertrophy and symptoms. Although it is
confirmed that

Leigh Syndrome Summary
In this study, the authors discovered a new gene mutation implicated in the onset of Leigh
syndrome, a neurodegenerative disease caused by lesions in multiple parts of the central nervous
system. The gene mutation was found in a girl with first–cousin parents. Since the girl did not
contain mutations of the existing candidate genes for Leigh disease, whole–exome sequence was
used to search for a novel homozygous mutation. It was discovered that the patient has a missense
mutation in SLC25A46, a gene that codes for a mitochondrial metabolite carrier protein. The
authors wanted to determine the role that mutant SLC25A46 has on causing Leigh syndrome. In
addition, the authors wanted to make clear the molecular functions of wild–type SLC24A46. Since
the onset of Leigh syndrome involves impairment ... Show more content on Helpwriting.net ...
Most candidate genes for Leigh syndrome code for the components and assembly proteins of the
oxidative phosphorylation complexes in the mitochondria (cite). While the SLC25A46 protein is
somehow involved in the assembly of the complexes, it is more directly involved in mitochondrial
morphology. As a result, this study is one of the few examples where a gene not directly associated
with oxidative phosphorylation can lead to Leigh syndrome. While the study connects the
SLC25A46 gene to Leigh syndrome, it did not do much to investigate how the mutant gene lead to
impairments in oxidative phosphorylation. The only finding was that the mutation lead to defective
assembly of complex IV in the ETC. The authors could have further investigated SLC25A46's role
in complex IV assembly, leading to a better understanding of the mutant protein's impact and the
normal protein's functions. In addition to connecting SLC25A46 to Leigh syndrome, this study's
investigation in the mutant gene's loss of function elucidates the various roles that wild–type
SLC25A46 has in the mitochondria. Other studies

Galactocerebrosidase Enzyme
Galactocerebrosidase enzyme (GALC) is an enzyme with very low activity, it is a lysosomal acid
hydrolase or a lysosomal catabolism that stimulate the removal of a monosaccharide sugar which is
galactose that is found in galactosylceramide or galactocerebroside (GalCer) or anything descendant
from ceramide. Galactocerebroside is a marker for oligodendrocytes in the brain, regardless of
whether they shape myelin. It is encoded by a specific gene which is (GALC) which is is formed in
the endoplasmic reticulum (ER)–Golgi complex after which it is transferred via the mannose–6–
phosphate pathway to the lysosome. If a missense mutation happened in this gene, it will affect on
the Galactocerebrosidase enzyme. This mutation that happens exactly on chromosome 14 (14q31)
that encompasses 17 exons, will cause the gene to be unstable or misfolding which will ... Show
more content on Helpwriting.net ...
The best one was the twitcher mouse model which occurring human krabbe disease that is caused by
a mutation in galactocerebrosidase gene. Mutation analysis of the human GALC gene was facilitated
by the cloning and sequencing of GALC cDNA (5). Mutation analysis of the human GALC gene
was facilitated by the cloning and sequencing of GALC cDNA . This allowed DNA obtained from
Krabbe affected people to be sequenced and analysed against the normal GALC gene. To date there
have been over forty mutations identified that cause the galactosylceramidase deficiency of Krabbe
disease .The most common mutation in the European population is a 30kb deletion which is
associated with a C to T transversion at cDNA position 502. The large 30kb deletion affects the
production of galactosylceramidase since it removes a significant portion of the enzyme coding
region. This results in the cancellation of 5 amino acids and the insertion of 2 amino acids which
impacts on the quaternary structure of the

Brca1 Mode Of Inheritance
1) BRCA1 is a gene that produces tumor suppression proteins which play critical roles in DNA
repair, cell cycle checkpoint control, and maintenance of genomic stability. Inherited mutated
BRCA1 causes DNA damage to not be repaired properly and these cells can then form genetic
alterations leading to female breast cancer (Easton 1999). Breast cancer is a disease where
malignant cancer cells form in the tissue of the breast and invade surrounding tissues and spread.
2) The mode of inheritance is autosomal dominance. This trait is still being studied and many
believe that breast cancer from BRCA1 is a multifactorial form of inheritance.
3) There was a large race for the cloning of BRCA1 gene and the most common way of cloning
included: Miki

Shwachman-Diamond Bodian Syndrome Summary
The article I read discussed a genetic disease known as Shwachman–Diamond–Bodian syndrome
otherwise known by its abbreviation SDS. The characteristic dysfunction of the disease itself is
weakened bone marrow functionality noted by an insufficiency within the pancreas causing
malabsorption of nutrients. In most severe cases, congenital thoracic dystrophy may be noted. In the
case of this article the authors use a new born baby to discuss the findings about and the expressions
of shwachman–diamond–bodian syndrome.
The authors state that the clinical diagnosis for the disease was confirmed by conduction a whole
exome sequencing. With this sequencing they were able to detect multiple heterozygous mutations.
These mutations were: a missense variation ... Show more content on Helpwriting.net ...
There was a ratio of 4:1 male–to female for the development of the disease. Important to note was
that it was reported that the authors cannot give any real explanation for the male preponderance.
More specifically, genetic analysis showed the patient to be heterozygous and have a single–
nucleotide mutation at codon 41A>G. This mutation resulted the amino acid asparagine to be
switched out with serine. Furthermore, according to a few prediction programs noted within the
article it was shown that this substitution of serine could prove damaging. In more detail, the
aberrant splicing mentioned before was shown to cause an 8 base pair long deletion within the
shwachman–diamond–bodian syndrome gene.
Although much is still unknown about shwachman–diamond–bodian syndrome, the one thing that
has been emphasized is the importance of whole exome sequencing in new born children.
Specifically, in the case of the newborn this article was based one. With the whole exome
sequencing, further in the future doctors will be able to distinguish quickly and with accuracy
between varying clinically overlapping conditions. There is still much more to learn about the
mechanism of this mutation and the exact role the mutation plays on changing the functionality of
the proteins within the

Desbuquois Dysplasia Essay
Desbuquois dysplasia (DBQD) is an infrequent skeletal disorder with an autosomal recessive trait. 1
It is regarded as a kind of dysplasia in the group of dysplasias with multiple joint dislocations.6 This
is a heterogeneous disease that shows overlap between some skeletal dysplasia diseases. 1,7 Their
phenotype indicate short extremity before birth, frailty joint, round face, midface hypoplasia, and
prominent eyes.4 Moreover, two hallmarks of this disorder include "Swedish key" and
"hyperphalangy of the index finger".2 According to presence or absence of hand abnormality, this
family divides to two subfamilies Desbuquois dysplasia type 1 and type 2.(2,5,7)Although, further
patients seem to have normal hands, they demonstrate strange and unusual hand changes that are
named "Kim variant" and are currently considered as type 1 of DBQD. (4) ... Show more content on
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(1) DBQD1 has resulted from the mutation in calcium–activated nucleotidase 1 gene (CANT1).
Actually, CANT1 codes an enzyme that is a part of the apyrase family and takes part in hydrolyzing
UDP. In fact, UDP, GDP, and UTP are the substrates of CANT1 and play a role in the signaling
pathways. (5) Bui et al. (2014) discovered other patients who suffered from DBQD2, carried
missense or nonsense mutations of XYLT1. 3 This gene encodes Xylosyltransferase 1 is responsible
for synthesizing the proteoglycan (PG). The structure of proteoglycan has been formed than a core
protein with one or more glycosaminoglycan (GAG) chains.

Primary Lymphedema Paper
Primary lymphedema occurs due to an intrinsic, most of the time genetic, aberration in the
lymphatic vasculature. Over the past decade, some of the key genetic factors leading to primary
lymphedema have been elucidated. In 2013, Connel and his colleagues created a clinical algorithm
for the diagnosis of primary lymphatic dysplasia [Figure 3.0].23 The figure demonstrates nine causal
mutations linked to primary lymphedema and we will briefly discuss some of these.
3.1 Milroy Disease
Milroy disease is a form of primary lymphedema, which presents with progressive swelling of the
face and lower extremities.24 It is characterized by the absence or marked diminution of lymphatic
vessels.25 Some cases have been associated with missense mutations in vascular endothelial growth
factor receptor 3 receptor tyrosine kinase (VEGFR3).26 The underlying pathology for this disease is
not the mere absence of initial lymphatic capillaries but the inadequacy of initial lymphatic fluid
absorption.3
3.2. Hennekam Syndrome
Hennekam syndrome, a rare autosomal recessive disorder, is characterized by lymphangiectasia
along with mental retardation.27 Limb and facial edema may be apparent at ... Show more content
on Helpwriting.net ...
Occurrence of lymphedema and distichiasis at puberty comprise the clinical diagnostic criteria.31 In
LDS, germline mutations in forkhead transcription factor C2 (FOXC2) gene mutations have been
implicated.31 This gene is integral in the development of lymphatic vasculature.32 In patients with
FOXC2 mutation, 100% will have superficial vein incompetence while a third will have deep vein
incompetence.33 The resulting venous stasis explains the edema. In a very recent study, even
mutations FOXC1 were noted to cause abnormal lymphatic vessel morphogenesis.34 This discovery
recognizes both FOXC1 and FOXC2 as fundamental controllers of lymphangiogenesis and
demonstrates another potential target for the management of

The Genetic Disease And Disorders
Cellular Biology Paper There are many genetic diseases and disorders in the world these days, some
of which are stranger or more unique then others. One such unique genetic disease is Congenital
Insensitivity to Pain with Anhidrosis or CIPA for short. This particular genetic disease causes people
who have to it to not be able to feel pain or even differentiated between hot or cold. As well as be
unable to sweat, because of the anhidrosis. This genetic condition is also known as hereditary
sensory and autonomic neuropathy type IV, but in this paper it will only be referred to as CIPA.
Congenital insensitivity to pain with anhidrosis, CIPA, is an inherited disorder of the nervous
system, which causes people to have to be unable to have ... Show more content on Helpwriting.net
...
It is very difficult for them because they have to be constantly checking them selves to make sure
that they haven't been cut or injured, especially in the mouth area and their limbs. The odds of
someone being born with this condition are about 1 in 125 million. So it is definitely not a very
common condition that many doctors would see. Doctors have however been able to identify the
gene mutation responsible for causing CIPA, it is the gene encoding the Neurotrophic Tyrosine–
Kinase receptor (NTRK1 gene). It is mutated in a way that interferes and halts the
autophosphorylation process, therefore stopping signals of pain and temperature from being sent to
the brain. The neurotrophic Tyrosine–Kinase, receptor, type 1 gene (NTRK1) is actually a very
important gene in the human body. It is the main gene that provides the instructions for making
certain proteins (NTRK1 proteins) that are essential for the development and survival of nerve cells.
Especially the ones that transmit the information that is sent for pain, temperature and touch
(sensory neurons). Sensory neurons are often found with the NTRK1 protein on them, this is
because they act as a kinase; which is a type of enzyme that catalyzes the transfer of oxygen and
phosphate groups to proteins, which is called phosphorylation. NTRK1 activated when nerve growth
factor beta (NGFβ) binds to it and singles the

Genetics Is A Branch Of Biological Science
Genetics is a branch of biological science that focuses on the study of genes and inheritance from
parent to offspring. Genes are found in chromosomes embedded in a cell's nucleus and carry the
traits that a person will have. We inherit our traits from our parents through sexual reproduction,
when two gametes, a sperm from the father and an ovum from the mother, combine and produce a
zygote. Gametes form through meiosis, which results in each gamete having 23 chromosomes. This
results in the zygote having 46 chromosomes, which combine and result in the genetic make up of
the offspring. Genes can be described as a set of instructions for the body to follow during fetal
development and for the rest of its life. However, certain exogenous and endogenous factors can
contribute to errors in genes that can result in genetic mutations. Exogenous factors are
environmentally bases and can be from sunlight, radiation, or smoking. While, endogenous factors
are internal and originate from errors during DNA replication. Genetic mutations are defined as a
permeant change in a DNA sequence and can be put into two categories: hereditary or somatic.
Hereditary mutations are endogenous and arrive to the DNA sequence of an organism from the
parent causing it to be present in all the DNA in the organism's body. These mutations are
sometimes referred to as germline mutations as a result of their presence in the parent's gametes,
which transfer the mutation to the offspring's genetic code.

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