User:Bcheon1/sandbox

Hello and welcome to my sandbox!

Preliminary outline for Missense Mutation

A definition and general explanation of missense mutation.

Examples of possible mutations that are caused by altering the genetic code:

• Nonsense mutation
• Frameshift mutation
• Neutral mutation (This topic comes from Mutation)
• Silent mutation (This topic comes from Mutation)

Relationships with suppressors and other mutations:

• Intragenic suppression with Missense mutation
• Intergenic suppression

Missense mutation with a related genetic code table (the focused is on mammals).

• (Please refer to Figure #15-6 in the Watson et al. textbook, page 537)

Examples of genetic diseases resulting from missense mutations (and perhaps possible therapies):

• Sickle-cell Anemia
• SOD1(Superoxide dismutase) mediated ALS(Amyotrophic Lateral Sclerosis)
• Osteopetrosis (Inherited genetic disease that linked to CLCN7 gene) (PMID 23302420, PMC 3567968)
• And others. (We need to decide how many we are going to add under this example section.)

References/See Also

• From the list of preliminary references below, as they are referring in the main article.

/Mhk5600 (talk) 20:47, 13 March 2013 (UTC)

Hey Min, I didn't change much of the content but I made some small edits to clean up typographical errors as well as the language. Bcheon1 (talk) 21:56, 13 March 2013 (UTC)

Preliminary preparations for editing Missense Mutation

Initial References from Unit 5 for Missense Mutation

• Brubaker RR (2012). "Consequences of missense mutations in Yersinia pestis: efficient flow of metabolic carbon versus virulence". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 954: 31–8. doi:10.1007/978-1-4614-3561-7_4. ISBN 978-1-4614-3560-0. PMID 22782743.
• Rauch A, Wieczorek D, Graf E; et al. (November 2012). "Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study". Lancet. 380 (9854): 1674–82. doi:10.1016/S0140-6736(12)61480-9. PMID 23020937. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
• Macdonald RL, Kang JQ (December 2012). "mRNA surveillance and endoplasmic reticulum quality control processes alter biogenesis of mutant GABAA receptor subunits associated with genetic epilepsies". Epilepsia. 53 (Suppl 9): 59–70. doi:10.1111/epi.12035. PMC 3762703. PMID 23216579.{{cite journal}}: CS1 maint: date and year (link)

New References

• Aspberg A (December 2012). "The different roles of aggrecan interaction domains". J. Histochem. Cytochem. 60 (12): 987–96. doi:10.1369/0022155412464376. PMC 3527881. PMID 23019016.{{cite journal}}: CS1 maint: date and year (link)
  • This review describes different missense mutations in the aggrecan C-type lectin repeat.
  • These mutations are known to lead to two different human hereditary disorders: autosomal recessive aggrecan-type spondyloepimetaphyseal dysplasia and autosomal dominant familial osteochondritis dissecans.
  • This reference would be useful for describing other possible health effects resulting from this mutation.
• Mahdaviani SA, Hirbod-Mobarakeh A, Wang N; et al. (August 2012). "Novel mutation of the activation-induced cytidine deaminase gene in a Tajik family: special review on hyper-immunoglobulin M syndrome". Expert Rev Clin Immunol. 8 (6): 539–46. doi:10.1586/eci.12.46. PMID 22992148. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  • This paper describes a novel missense mutation that was found in one of the genes of two individuals with hyper-immunoglobulin M (HIGM) syndrome.
  • This is another example of a missense mutation resulting in a disease.
• Dzamko N, Halliday GM (October 2012). "An emerging role for LRRK2 in the immune system". Biochem. Soc. Trans. 40 (5): 1134–9. doi:10.1042/BST20120119. PMID 22988878.{{cite journal}}: CS1 maint: date and year (link)
  • This review article shows how missense mutations in LRRK2 (leucine-rich repeat kinase 2) contribute to autosomal dominant Parkinson's disease.
  • This is like the above two but Parkinson's disease is more well known and probably more relevant.
• Greggio E (October 2012). "Role of LRRK2 kinase activity in the pathogenesis of Parkinson's disease". Biochem. Soc. Trans. 40 (5): 1058–62. doi:10.1042/BST20120054. PMID 22988865.{{cite journal}}: CS1 maint: date and year (link)
  • This is another review talking about missense mutations in LRRK2.
  • LRRK2 seems to get quite a bit of focus because of it's connection to Parkinson's disease so this may make a good topic in our article.
• Mohajeri MH, Giese KP (August 2012). "Two selected models of missense mutations in mice for the study of learning behaviour". Brain Res. Bull. 88 (5): 429–33. doi:10.1016/j.brainresbull.2011.12.003. PMID 22214603.{{cite journal}}: CS1 maint: date and year (link)
  • This review talks about the impacts of missense mutations on learning and memory in mice.
  • The review then talks about how this relates to humans.
  • This might be a good example of how small missense mutations can result in changes in phenotype.
• Rashid BM, Rashid NG, Schulz A, Lahr G, Nore BF (2013). "A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series". J Med Case Rep. 7 (1): 7. doi:10.1186/1752-1947-7-7. PMC 3567968. PMID 23302420.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  • Inherited genetic disease caused by missense mutation.
  • The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan.
  • Mutated gene may be a dominant-negative impact on the protein.
• Minde DP, Anvarian Z, Rüdiger SG, Maurice MM (2011). "Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?". Mol. Cancer. 10: 101. doi:10.1186/1476-4598-10-101. PMC 3170638. PMID 21859464.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  • Listed reference articles from a current missense mutation

/Mhk5600 (talk) 16:28, 12 March 2013 (UTC)

Potential Suitably-Licensed Images

Types of mutations 01

Types of mutations 01-fr

Amino-acid biochemical properties

Nonpolar

Polar

Basic

Acidic

Termination: stop codon

Standard genetic code (NCBI table 1)

1st base	2nd base								3rd base
	U		C		A		G
U	UUU	(Phe/F) Phenylalanine	UCU	(Ser/S) Serine	UAU	(Tyr/Y) Tyrosine	UGU	(Cys/C) Cysteine	U
	UUC		UCC		UAC		UGC		C
	UUA	(Leu/L) Leucine	UCA		UAA	Stop (Ochre)[B]	UGA	Stop (Opal)[B]	A
	UUG[A]		UCG		UAG	Stop (Amber)[B]	UGG	(Trp/W) Tryptophan	G
C	CUU		CCU	(Pro/P) Proline	CAU	(His/H) Histidine	CGU	(Arg/R) Arginine	U
	CUC		CCC		CAC		CGC		C
	CUA		CCA		CAA	(Gln/Q) Glutamine	CGA		A
	CUG		CCG		CAG		CGG		G
A	AUU	(Ile/I) Isoleucine	ACU	(Thr/T) Threonine	AAU	(Asn/N) Asparagine	AGU	(Ser/S) Serine	U
	AUC		ACC		AAC		AGC		C
	AUA		ACA		AAA	(Lys/K) Lysine	AGA	(Arg/R) Arginine	A
	AUG[A]	(Met/M) Methionine	ACG		AAG		AGG		G
G	GUU	(Val/V) Valine	GCU	(Ala/A) Alanine	GAU	(Asp/D) Aspartic acid	GGU	(Gly/G) Glycine	U
	GUC		GCC		GAC		GGC		C
	GUA		GCA		GAA	(Glu/E) Glutamic acid	GGA		A
	GUG[A]		GCG		GAG		GGG		G

^A Possible start codons in NCBI table 1. AUG is most common. The two other start codons listed by table 1 (GUG and UUG) are rare in eukaryotes. Prokaryotes have less strigent start codon requirements; they are described by NCBI table 11.

^{B ^ ^ ^} The historical basis for designating the stop codons as amber, ochre and opal is described in an autobiography by Sydney Brenner and in a historical article by Bob Edgar.

Inverse table for the standard genetic code (compressed using IUPAC notation)

Amino acid	DNA codons	Compressed		Amino acid	DNA codons	Compressed
Ala, A	GCU, GCC, GCA, GCG	GCN		Ile, I	AUU, AUC, AUA	AUH
Arg, R	CGU, CGC, CGA, CGG; AGA, AGG	CGN, AGR; or CGY, MGR		Leu, L	CUU, CUC, CUA, CUG; UUA, UUG	CUN, UUR; or CUY, YUR
Asn, N	AAU, AAC	AAY		Lys, K	AAA, AAG	AAR
Asp, D	GAU, GAC	GAY		Met, M	AUG
Asn or Asp, B	AAU, AAC; GAU, GAC	RAY		Phe, F	UUU, UUC	UUY
Cys, C	UGU, UGC	UGY		Pro, P	CCU, CCC, CCA, CCG	CCN
Gln, Q	CAA, CAG	CAR		Ser, S	UCU, UCC, UCA, UCG; AGU, AGC	UCN, AGY
Glu, E	GAA, GAG	GAR		Thr, T	ACU, ACC, ACA, ACG	ACN
Gln or Glu, Z	CAA, CAG; GAA, GAG	SAR		Trp, W	UGG
Gly, G	GGU, GGC, GGA, GGG	GGN		Tyr, Y	UAU, UAC	UAY
His, H	CAU, CAC	CAY		Val, V	GUU, GUC, GUA, GUG	GUN
START	AUG, CUG, UUG	HUG		STOP	UAA, UGA, UAG	URA, UAR

• Appending potential images coming.../Mhk5600 (talk) 14:53, 12 March 2013 (UTC)

Inline Citation Practice (Unit 5 Assignment)

Pubmed Article #1

The title of my first PubMed article is: Acute depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate impairs specific steps in endocytosis of the G-protein-coupled receptor.

The primary goals were to investigate the role and importance of Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] in the plasma membrane on the endocytic process of GPCRs and to determine whether depleting PtdIns(4,5)P(2) would disrupt this process. Three different GPCRs were studied including: luciferase-labeled type 1 angiotensin II (AT1R), type 2C serotonin (5HT2CR) and β(2) adrenergic (β2AR) receptors. The authors found that when they depleted PtdIns(4,5)P(2), there was generally a significant inhibition in the number of GPCRs in early endosomes. This study confirmed that GPCRs rely on PtdIns(4,5)P(2) in their endocytic pathways. Delivery of one of the GPCRs to early endosomes for example was completely stopped when PtdIns(4,5)P(2) was depleted.

Pubmed Article #2

The title of my second PubMed article is: MCAK activity at microtubule tips regulates spindle microtubule length to promote robust kinetochore attachment.

The main goal of this study was to see if MCAK’s (mitotic centromere-associated kinesin) effect on dynamic microtubule plus ends is the reason shorter spindles are observed during meiotic spindle assembly when MCAK levels are raised. The authors tested this in human mitotic cells by depleting MCAK levels using siRNA and then observing the spindle assembly in the cells. The authors found that the tip-tracking activity for MCAK was played an important role in stopping the centrosomes from separating when bipolar spindles were being assembled. The significance of this was clarified when the authors also monitored kinetochore attachment. It turned out that when cells were lacking MCAK, the spindle fibers that were made had “excessively” long microtubules that were not kinetochore related.