Mutations of nucleotide sequences and chromosome abnormalities Genetic Mutations Mutations of nucleotide sequences and chromosome abnormalities

Things you should know…. How do you define “mutation”? How might a mutation of a genotype affect a phenotype? Mutations come about by… Typo mistakes during DNA synthesis -- about 120,000 each replication. Environmental factors such as radiation and mutagenic chemicals Mutations-- Good or Bad? Neutral? How are mutations passed on?

Two Major Types of Mutations Nucleotide Mutations Chromosome Mutations

Two Major Types of Nucleotide Mutations Point Mutations Substitutions Non-sense Missense Silent Mutations Frameshift (insertions/deletions)

Point Mutations Substitutions In a base substitution mutation, a single base pair is incorrectly matched. Nonsense mutations. Missense mutations. Silent mutations

Hemoglobin

Frameshift Mutations Mutations that change the reading of the triplet code by inserting (insertions) or deleting (deletions) one or two nucleotides are known as frameshift mutations. Generally, the amino acid(s) coded for after the point of deletion or insertion are different from those intended, resulting in a missense mutation. If the frameshift results in stop code, the mutation is a nonsense mutation.

Causes of Genetic Mutations Spontaneous Mutations Result from errors in DNA duplication, recombination or DNA repair are naturally occurring Induced Mutations Mutagens UV Light/Free Radicals

Two Major Types of Mutations Chromosome Mutations Non-disjunctions aneuploidy Trisomy Monosomy Changes in chromosome structure Deletions of chromosomes or parts of chromosomes Duplications Inversions Translocations

Chromosome Mutations Non-disjunctions During meiosis I or II, homologous chromosomes do not separate properly. Here, one gamete receives two of the same type of chromosome while the other gamete receives no copy. If one of these gametes are chosen for fertilizaton then the offspring will have an aneuploidy, or a abnormal chromosome number. If the zygote receives three copies after fertilization (2 mutant and one normal) we call this 2n+1 or a trisomy If the zygote only receives one copy (one is missing), we call this a monosomy, 2n-1. One of the most familiar trisomys is trisomy 21 which causes Down’s Syndrome.

Trisomy 21

Changes in Chromosome Structure Deletions A chromosomal deletion is a loss of the chromosome or a large portion of the chromosome (generally a fragment without a centromere). The remainder of the chromosome, with the centromere intact, contains the deletion. Many deletions cause serious problems and can be lethal, since critical genes are missing. Duplications A deleted chromosome fragment can attach to its homologue, thereby duplicating a region of genes on the chromosome to which it attaches. Or, as happens in some genes, a segment of the gene or chromosome undergoes multiple repetitions, so that several copies are located on the chromosome.

Gene Transfer Gene transfer is when genes from one chromosome (or even an organism) are transferred to a different chromosome or rearranged within a chromosome. There are two common gene transfers: inversions and translocations (or transpositions). Inversions For an inversion, a small group of genes can have their order reversed on the chromosome so that a gene sequence that should be A-B-C-D-E-F-G-H is changed to A- B-F-E-D-C-G-H instead. This results in part of the DNA being "backwards" and may not be able to be transcribed. Moreover, during meiosis, inversions do not pair and form uneven, internal loops that cannot do crossing over without losing genes and duplicating genes on chromatids. Many gametes are not viable after inversions.

Gene Transfer Translocation A gene can be transposed or translocated (moved) to a different location along the gene, so that the sequence might read A-B-C-E-F-G-D rather than A-BC- D-E-F-G. Since many genes are read in sequence, altering the sequence may affect the ability to read a gene. Translocation can also involved transferring a part of a chromosome to a different, non-homologous chromosome. Reciprocal translocations involve exchange of genes between non-homologous chromosomes.

Nucleotide Repeats An unusual duplication is the multiple repeats of specific DNA triplets, called trinucleotide (or triplet) repeats. They are also tandem repeats because they occur in sequence along the chromosome. The trinucleotide repeat occurs within some abnormal genes, and is responsible for several genetic disorders. Trinucleotide repeats were first reported in the genetic disease, the fragile X syndrome, a developmental disorder leading to mental retardation. In fragile X, the leader sequence (CGG repeats) is repeated hundreds of times. Fragile X is a major cause of mental retardation.

Causes of Genetic Mutations Spontaneous Mutations Result from errors in DNA duplication, recombination or DNA repair are naturally occurring Induced Mutations Mutagens UV Light/Free Radicals