Interested in finding out more about mutation

[Euphoriet]

I am interested in finding out more about mutation but so far I haven't found much on the topic...

What would be a place to start if you are only familiar with the basics of DNA replication... translation.. transcription...

I don't know much on the subject... thanks.

News reguarding mutation would also be cool, so far I have only found an article on google news that interests me:

http://www.webindia123.com/news/showdetails.asp?id=36643&cat=Health

 

[iansmith]

This page is a good intro to various time of mutations and repair mechanism
Mutation, Mutagens, and DNA Repair

This page has good glossary about mutation related term
http://a-s.clayton.edu/hampikian/b4201/Hartlvocab/GeneticsCh7.doc

If you need more detail info just ask what you want to known

 

[Euphoriet]

Ok thanks I'll check them out.

 

[Euphoriet]

Umm I was wondering what the most common mutations are in todays new borns?

Another Question:

Are we actually able to reverse certain types of mutations at this moment with the current technology we have?

 

[iansmith]

Umm I was wondering what the most common mutations are in todays new borns?

There no study for that but my guess is that most are either coming from the parents gametes or an external mutagenic source migth. I doubt recplication errors occurs often in the baby.

Are we actually able to reverse certain types of mutations at this moment with the current technology we have?

There migth be photoreactivation for mutation cause by U.V. or agent that cause pyrimidine dimer. Not much study has been done on this and it would only work on the skin. The only other possible techniques would be genetic engineering which would replace the whole gene or complement cells

 

[Euphoriet]

Umm I see so I guess.. that would be a no to my second question... which is what I thought.

For my first question.. I should have asked.. What is a well known decease caused by mutation?.. sickle cell anemia?

 

[iansmith]

You got sickle cell, tay-sach, cystic fibrosis, some forms of juvenile diatbetes, and the list goes on.

 

[Moonbear]

Actually, sickle cell isn't a mutation, at least not a recent one. I don't think tay-sach is either. I would need to check on cystic fibrosis and type I diabetes. They are recessive traits present in the human genome. At least in the case of sickle cell, the heterozygotes are healthy, actually have a better resistance to malaria, which provides a beneficial selection pressure to preserve that allele in the genome (more heterozygotes survive a malaria epidemic than those without that allele...at least in the days before modern medicine). It's those who inherit the sickle cell allele from both parents and are homozygous that are ill.

It's hard to know what the common mutations are in newborns. A lot of mutations can have no detectable phenotype (doesn't necessarily mean they don't do anything, just we don't know what it is and don't look for it, but some mutations are silent). My guess is those might be the most common. Many other mutations are embryonically lethal (affect development, so a miscarriage would occur), so those don't affect newborns because they never develop far enough to be born alive. However, the few that result in obvious birth defects are probably the ones that get most attention. I don't know if there are any that are commonly occurring. Theoretically, mutations would be random, so none should occur more often than others, but there may be some genes more susceptible to mutation due to their location on the chromosomes?

 

[Monique]

A mutation is when DNA is changed in such a way that the genetic message carried by the gene is changed. Since sickle cell anemia is the condition where the HbS gene is altered and causes sickled hemoglobin to be produced, so yes, it would be a mutation. Only when the prevalence of the mutation reaches sufficient high levels is a population, would it be described as a trait.

I think that Moonbear is thinking about de-novo mutations, which are generated new and not passed on from a previous generation? If you like to know some diseases which arise from that, you'd have to look at ones where patients do not reach the age of reproduction or where they are unable to reproduce.

 

[Monique]

Umm I was wondering what the most common mutations are in todays new borns?

That entirely depends on the population you are looking at. Disease frequencies are different for populations with different histories. For instance, in malaria-infested populations, sickle cell anemia would probably be the most prevalent trait/mutation-caused disease you'd see.

Another Question:

Are we actually able to reverse certain types of mutations at this moment with the current technology we have?

Yes, gene therapy would be the example with the model disease of SCID (severe combined immune deficiency). The disease is caused due to adenosine deaminase deficiency, the gene can be put back into a patient's cells with the use of virusses.

 

[iansmith]

Tay-Sachs is an autosomal recessive genetic disorder resulting from mutation of the HEXA gene encoding the alpha-subunit of the lysosomal enzyme, alpha-N-acetylhexosaminidase.

http://www-personal.umd.umich.edu/~jcthomas/JCTHOMAS/1997 Case Studies/S. Bergeron.html

EXAMPLE: sickle-cell disease The replacement of A by T at the 17th nucleotide of the gene for the beta chain of hemoglobin changes the codon GAG (for glutamic acid) to GTG (which encodes valine). Thus the 6th amino acid in the chain becomes valine instead of glutamic acid.

Here is a sampling of the more than 1000 different mutations that have been found in patients with cystic fibrosis. Each of these mutations occurs in a huge gene that encodes a protein (of 1480 amino acids) called the cystic fibrosis transmembrane conductance regulator (CFTR). The protein is responsible for transporting chloride ions out of cells. The gene encompasses over 6000 nucleotides spread over 27 exons on chromosome 7. The numbers in the mutation column represent the number of the nucleotides affected. Defects in the protein cause the various symptoms of the disease. Unlike sickle-cell disease, then, no single mutation is responsible for all cases of cystic fibrosis. People with cystic fibrosis inherit two mutant genes, but the mutations need not be the same.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Mutations.html

For example, it is now known that the insulin-dependent diabetes mellitus (IDDM1) locus on chromosome 6 may harbor at least one susceptibility gene for Type 1 diabetes. Exactly how a mutation at this locus adds to patient risk is not clear, although a gene maps to the region of chromosome 6 that also has genes for antigens (the molecules that normally tell the immune system not to attack itself)

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.137

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR/ABCC7). Despite the extensive and enduring efforts of many CF researchers over the past 14 years, up to 30% of disease alleles still remain to be identified in some populations. It has long been suggested that gross genomic rearrangements could account for these unidentified alleles. To date, however, only a few large deletions have been found in the CFTR gene and only three have been fully characterized.

http://www.ncbi.nlm.nih.gov:80/entr...ve&db=pubmed&dopt=Abstract&list_uids=15024729

Sickle cell disease is caused by a mutation in the beta-globin chain of the haemoglobin molecule. Sickle haemoglobin, the result of this mutation, has the singular property of polymerizing when deoxygenated. Exactly how normal tissue perfusion is interrupted by abnormal sickle cells is complex and poorly understood. Despite genetic identity at the site of the sickle haemoglobin mutation, all patients with sickle cell anaemia are not affected equally by this disease. Secondary genetic determinants and acquired erythrocyte and vascular damage are likely to be central components of the pathophysiology of sickle cell anaemia.

http://www.ncbi.nlm.nih.gov:80/entr...ve&db=pubmed&dopt=Abstract&list_uids=10872477

The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs)

http://www.ncbi.nlm.nih.gov:80/entr...ve&db=pubmed&dopt=Abstract&list_uids=14727180

 

[Monique]

Actually OMIM (Online Mendelian Inheritance in Man) would be the place to look up this kind of information http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM it used to be strictly about mendelian inheritance, but not it is mostly a collection of all genetic diseases known.

 

[Euphoriet]

Ok thanks I'll check it out guys and get back at you with more questions if I have any =-P

 

[Euphoriet]

sickle cell anemia .. heh is it a severe condition.. what exactly does it do?

 

[iansmith]

Check these web sites it contains some general information
http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/sca.shtml
http://www.mayoclinic.com/invoke.cfm?id=DS00324
http://kidshealth.org/parent/medical/heart/sickle_cell_anemia.html

 

[Euphoriet]

so apparently.. sickle cell anemia is not something I would use to explain DNA replication, transcription and translation .. since it is an inherited disease.. and not a "real" mutation... what would be the next best thing to explain dna replication... protein synthesis that IS a mutation =-/.

 

[iansmith]

Sickle cell anemia is a "real" mutation, but it occurs several hundreds years ago. It was select for in certain population because it had a certain benefit. That is why it is inherited. You DNA is migth have mutation and migth be pass on to your offspring.

The best example to explain mutation that are not inherited in an indvidual would be cancer.

 

[Euphoriet]

WHat about doing it with an unknown mutation

 

[iansmith]

What do you mean by doing it with an unknown mutation?

 

[Monique]

I think he means a de novo mutation, a mutation that was introduced in the gamete. The disease phenotype could be anything really, it all depends in what gene the mutation occurred. It would have to be a dominant trait though, since only one allele is affected (assuming no mutation was present in the other allele).

You could use sickle cell anemia though, but explain that the mutation occurred a long time ago (it probably is known how long) and you could explain how that mutation also proved beneficial and stayed in the population.

 

[iansmith]

It would have to be a dominant trait though, since only one allele is affected (assuming no mutation was present in the other allele).

Unless it occurs on the X or Y chromosome and the newborn is a boy.

 

[Euphoriet]

I mean a mutation that is not spread through generations.. not inherited.. but just a mistake I guess in DNA that has just occurred and only affects the new born baby and the parents didnt carry any alleles for it...

 

[selfAdjoint]

So the baby will grow up with it as one of its alleles and will exhibit whatever characteristics derive from that. For example mutations in the BRCA1 gene expose women to a higher risk of breast cancer. And since the mutation is now a part of that individual's genome, it can be passed on to the individual's descendents. For example Queen Victoria was a late child of her father, King William IV. It is thought that this man had suffered a mutation during his long life which he passed to Victoria, and she passed to her descendents, causing them to suffer with a bleeding disease that much affected the history of Europe, since Victoria's children and grandchildren married into most of the royal families of Europe.

 

[Monique]

I mean a mutation that is not spread through generations.. not inherited.. but just a mistake I guess in DNA that has just occurred and only affects the new born baby and the parents didnt carry any alleles for it...

Right, de novo = new. This is how every mutation gets introduced. I wonder how many mutations are introduced in every newborn? There are 3 billion bases, only less than 2% are genes (I believe?).. a lot of room for error.

 

[Jeebus]

Right, de novo = new. This is how every mutation gets introduced. I wonder how many mutations are introduced in every newborn? There are 3 billion bases, only less than 2% are genes (I believe?).. a lot of room for error.

Did you hear that Japanese scientists created two artificial bases a while ago for a new in vitro species?

I'll find the link if you are interested.

 

[Monique]

You mean modified bases? Yeah, they've been making those.. what did the Japanese use them for? There are a few for the applications I know, one is for sequencing GC rich regions, where the regular G is replaced for one with a lower melting temperature. The other is where they modified RNA bases so that it can be applied in making RNAi probes that don't degrade as fast as normal RNA would.