Bio Chapter 15

somatic mutation

-mutations that occur in body cells. -These mutations are passed on to the daughter cells during mitosis, and to the offspring of those cells in turn, but are not passed on to sexually produced offspring -patches of skin cells not passed on to children

germ line mutation

-mutations that occur in the cells that give rise to gametes. -A gamete with the mutation passes it on to a new organism at fertilization. -The new organism will have the mutation in every cell of its body and will pass the mutation on to all of its progeny.

somatic cell gene therapy

-new gene is inserted into somatic cell involved in disease -can be ex vivo or in vivo

thalassemia

-nonsense mutation in Mediterranean populations that drastically shortens the β-globin subunit. -Shortened proteins are usually not functional; however, if the nonsense mutation occurs near the 3′ end of the gene, it may have no effect on function.

chromosomal mutations

-occur when chromosomes break during replication -include deletions, duplications, inversions, and translocations -can be caused by severe damage to chromosomes caused by mutagens or errors in chromosome replication

induced mutations

-occur when some agent from outside the cell - a mutagen - causes a permanent change in DNA -NO2 is an example since it causes the deamination reaction -some chemicals add groups to nucleotides altering their ability to base pair -radiation is another cause of this type of mutation

deletion

-occurs by a removal of a part of the genetic material -can occur if a chromosome breaks at two points and then rejoins, leaving out the DNA between the breaks

spontaneous mutations

-permanent changes in the genetic material that occur without any outside influence -example of this is when the rare cytosine tautomer is expressed instead pairs with A instead of G -can also be caused by deamination reaction that removes an amino group from cytosine -DNA polymerase can make errors too -Meiosis is not perfect. Therefore the failure of chromosomes to separate may cause this.

genetic markers

-reference point for gene isolation -SNPs and STPs are examples of this -key is that two genes are located near each other on the same chromosome, they are usually passed on together from parent to offspring

multifactorial

-refers to how many common phenotypes including those that cause disease are caused by the interactions of many genes and proteins with one or more factors in the environment

chromosomal abnormalities

-result from a gain or loss of complete chromosomes -example is the fragile-X syndrome, which is a restriction in the tip of the X chromosome that can result in mental retardation

Short Tandem Repeats (STRs)

-short, repetitive DNA sequences that occur side by side on the chromosomes, usually in non coding regions -These repeated patterns are inherited

in vivo somatic cell gene therapy

-the gene is inserted directly into the patient -targets the appropriate cells

restriction digestion

-the process in which a restriction enzyme breaks the bonds between nucleotides

transversion mutation

-the substitution of a purine for a pyrimidine or vise versa -A-->C

transition point mutation

-the substitution of one purine for the other purine or one pyrimidine for the other

cigarette smoke

-this causes cancer due to somatic cells in the lung and throat's increased exposure to benzopyrene and other carcinogens

reverse genetics

-when a clinical phenotype is first related to a DNA variation and then the protein involved is identified

translocation

-when a segment of a chromosome breaks off and becomes attached to a different chromosome -involve reciprocal exchanges of chromosome segments -Down syndrome involves this on chromosome 21

reversion mutations

-when mutations are reversed -they are re-mutated a second time so that the DNA reverts to its original sequence or to a coding sequence that results in the non-mutant phenotype

frame-shift mutation

-when one or two nucleotides are inserted into, or deleted from, a sequence of DNA -alter the reading frame in which the three-base codons are read during translation -result in a completely different amino acid sequence

ex vivo somatic cell gene therapy

-when target cells are removed from the patient, given the new gene, and then reinserted into the patient

expanding triplet repeats

-when triplets are repeated 200-2000 times -result in numbers diseases such as Huntingtons and Fragile-X -believed that DNA polymerase slips after copying a repeat and then falls back to copy it again

germ line gene therapy

-where a new gene is inserted into a gamete/fertilized egg -leads to all cells of the adult to carry the new gene

recognition sequence/restriction site

-where the restriction enzyme cleaves DNA -most are 4-6 base pairs long -because of its unique structure it can be recognized by a particular restriction enzyme -DNA protects their DNA with methyl groups to prevent binding by the restriction enzymes

Adeno-associated virus

-widely used in human gene therapy clinical trials -has a small genome that allows splicing in of a human gene -is used because uptake of DNA into eukaryotic cells is a rare event

phenylketonuria (PKU)

The disease results from an abnormality in a single enzyme, phenylalanine hydroxylase (PAH), which catalyzes the conversion of dietary phenylalanine to tyrosine -This enzyme is not active in the livers of PKU patients, leading to excesses of phenylalanine and phenylpyruvic acid in the blood. -A common mutation in the nucleotide sequence is a missense mutation that results in tryptophan instead of arginine at position 408 in the polypeptide chain

Methylation

-most common in cytosines -important role in gene regulation

Fragile X syndrome

-About one-fifth of all males who have the this abnormality are phenotypically normal, as are most of their daughters. -But many of those daughters' sons are mentally retarded. -In a family in which this disorder appears, later generations tend to show earlier onset and more severe symptoms of the disease. It is almost as if the abnormal allele itself is changing—and getting worse. -gene responsible contains a repeated triplet -in mentally retarded people with this, repeated sequence 200 to 2000 times

missense mutation

-a base substitution that changes the genetic code such that one amino acid substitutes for another in a protein -may result in a defective protein, but often it has no effect on the protein's function -might reduce the functional efficiency of a protein rather than completely inactivating it -may also lead to a gain of function mutation -Example: sickle-cell disease. The sickle allele differs from the normal allele by one base pair, resulting in a polypeptide that differs by one amino acid from the normal protein.

mutation

-a change in the nucleotide sequence of DNA that can be passed on from one cell, or organism, to another.

transposon

-a form of DNA that can insert itself into genes and cause mutations -widespread in both prokaryotic and eukaryotic genomes -a DNA sequence of a few hundred to a few thousand base pairs that can move from one position in the genome to another. -It usually carries genes that encode the enzymes needed for this movement.

Mutative benefits

-a mutation in a somatic cell may benefit the organism immediately. -a mutation in a germ line cell may have no immediate selective advantage to the organism, but it may cause a phenotypic change in the organism's offspring.

conditional mutation

-affects phenotype only under certain restrictive conditions and is not detectable under other, permissive conditions. -temperature is an example of a condition that may change the stability of proteins

loss of function mutation

-affects protein function -Such a mutation may cause a gene to not be expressed at all, or the gene may be expressed but produce a protein that no longer plays its cellular role, such as its catalytic function if it is an enzyme. -almost always show recessive inheritance in diploid organisms, because the presence of one wild-type allele will usually result in sufficient functional protein for the cell. -codes for a nonfunctional protein

duplication

-can be produced at the same time as a deletion and can occur if homologous chromosomes break at different positions and then reconnect to the wrong partners -results in one chromosome with a deleted segment and one chromosome with two copies of the same segment

retrovirus

-can insert their genetic information into the host cell's genome -this can cause loss of function mutation in that gene -viral DNA often remains in the host genome and is passed on from one generation to the next (this is referred to as a endogenous one of these)

inversion

-can result from the breaking and rejoining of a chromosome where a segment of DNA becomes "flipped" so that it runs in the opposite direction from its original orientation

point mutation

-changes in single nucleotides -the addition or subtraction of a single nucleotide or the substitution of one nucleotide base for another

restriction enzymes

-cut double stranded DNA into smaller, noninfectious fragments -these enzymes break the bonds of the DNA backbone between the 3' hydroxyl group of one nucleotide an the 5' phosphate group of the next one

DNA testing

-direct analysis of DNA for a mutation and it offers the most direct and accurate way of detecting an abnormal allele -image 15.18 shows it perfectly

sickle cell

-disease is caused by a recessive, missense mutation. -two α chains and two β chains—as well as the pigment heme. -In sickle-cell disease, one of the 146 amino acids in the β-globin polypeptide chain is abnormal: at position 6, glutamic acid is replaced by valine. -glutamic acid may be replaced by lysine causing hemoglobin C -about 5 percent of all humans carry at least one missense point mutation in a β-globin allele.

silent mutation

-does not usually affect protein function -can be a mutation in a region of DNA that does not encode a protein, or it can be in the coding region of a gene but not affect the amino acid sequence -common, and they usually result in genetic diversity that is not expressed as phenotypic differences. -codes for a functional protein

TP53 Gene Mutation

-example of missense mutation that causes a gain of function -codes for a tumor suppressor, a protein that inhibits the cell cycle -this mutation would give this gene an oncogenic (cancer causing) function

Gene therapy

-goal is to add a new gene that will be expressed in appropriate cells in a patient -approaches involve germ line gene therapy and somatic cell gene therapy

DNA finger printing

-identifies individuals based on difference in their DNA sequences -works best with sequences that are highly polymorphic (have a lot of alleles so they are more likely to be individualized)

Single nucleotide polymorphisms (SNPs)

-inherited variations involving a single nucleotide base -point mutations -if they occur in a restriction enzyme recognition site, very say to distinguish using PCR

nonsense mutation

-involves a base substitution that causes a stop codon -results in a shortened protein since translation does not occur beyond the point of mutation -if the mutation occurs near the 3' end of the gene it may have no effect on the function

DNA linkage analysis

-isolating a linkage to a SNP in order to determine the location of a defective gene

gain of function mutation

-leads to a protein with an altered function -codes for a protein with a new function -This kind of mutation usually shows dominant inheritance, because the presence of the wild-type allele does not prevent the mutant allele from functioning. -common in cancer