possibly affecting more than one gene (multi-gene level)
Changes in NUMBER
Monoploid number (2n 1)
Euploidy (multiples of n)
Polyploid (3n 4n 5n)
Triploid tetraploid pentaploid hexaploid
3 1. Polyploidy
Usually lethal in mammals
Does occur in some animals - Reproduction via parthenogenesis Flatworms leeches brine shrimp lizards salamanders salmonids
Polyploidy in plants much more common because it can be tolerated by plants can reproduce asexually Important role in the evolution of plants wheat 2n 14 28 42 chrysanthemum 2n 18 36 54 72 90 4 (No Transcript) 5 sympatric speciation e.g. polyploidy in plants..
Autopolyploidy due to meiosis error. Offspring can self fertilize.
2 different species mating produce a hybrid that is polyploid
The hybrid is fertile because the polyploid condition provides the homologous chromosomes for pairing during meiosis
only certain cells in the organism are polyploid
Liver cells plant tissue (stem)
larval gut tissue (mosquitos)
7 2. Aneuploidy the total is not an exact multiple of a set(2n /- x)
Caused by Nondisjunction failure of normal chromatid division during meiosis two chromosomes go to one pole none in the other.
Results in the wrong number of chromosomes.
Results in a gene imbalance
8 Fertilization of one of these affected gametes produces a zygote w/ either 3 members (trisomy) or only one member (monosomy) of the chromosome. 9 gene imbalance - THE problem
Aneuploids are more abnormal than polyploids why (polyploid plants are completely viable and usually bigger whereas in Drosophila the only aneuploids that survive are trisomics and monosomics for chromosome 4 the smallest chromosome)
Normal physiology of a cell depends on the proper ratio of gene products in the euploid cell.
The amount of expression is correlated with the number of genes in a cell
If 3 copies present 150 of the normal amount of protein will be made
If 1 copy present 50 of the normal amount of protein will be made
10 Nondisjunction responsible for Turners syndrome and Kleinfelters syndrome Turners syndrome produces sterile females with a normal of autosomes and 1 X chromosome (XO). These are the only human monosomics that survive Klienfelters syndrome individuals are trisomic XXY they are sterile males that are typically tall and thin and some degree of mental retardation. XYY trisomic males have mild mental retardation 11 Aneuploid Conditions in Humans Inherited disorders associated with aneuploidy. Trisomies and variations in the sex chromosomes result in mental retardation organ defects sexual immaturity etc. 12 Trisomy 21 abnormal creases Trisomy 18 diaphragmatic hernia Turners syndrome developmental abnormality polydactyly 13 Why is monosomy so bad
Monosomics for all human autosomes die in utero
Any deleterious recessive alleles present on monosomic autosome will be automatically expressed
14 B. Changes in chromosome structure
15 Deletion loop 16 1. Deletions
Spontaneous breakage and rejoining
Crossing over between repetitive DNA
Region w/centromere usually maintained during division the other part will be lost 17 Multigenic deletions
If both homologs have the same deletion then it will be lethal
If only on one homolog the deletion can uncover lethal recessives in the heterozygous condition
Psuedodominance when recessive alleles are expressed due to a deletion event
18 partial monosomy Caused by a heterozygous deletion of the tip of the p arm of chromosome 5 phenotype distinctive cat-like cry made by infants microencephaly moon-like face 19 2. Duplications
Extra copy of some particular region Rare and difficult to detect
Usually due to unequal crossing over during meiosis or through replication error prior to meiosis
Not as problematic as deletions but some problems are associated
Bar eye in Drosophila (gene imbalance)
20 (No Transcript) 21 3. Inversions
Region breaks rotates 180 degrees and rejoins
Generally viable and show no abnormalities at the phenotypic level
Paired homologs form an During synapsis one chromosome must twist into a loop to pair up w/the genes on the other 22 Types of inversions 1) Paracentric centromere outside of the inversion Cross over products dicentric and acentric chromosome 2) Paricentric inversion spans centromere Cross over products duplication and deletion 23 During meiosis homologs still pair up even w/inversions -Inversion loop makes this possible 24 Crossing over produces affected chromatids Duplication Deletion events 25 (No Transcript) 26 4. Translocation-movement of chromosomal fragments to a new location.
Semisterility an organism that is heterozygous for a reciprocal translocation usually produces about half as many offspring as normal
due to difficulty in chromosome segregation in meiosis.
Translocation cross because of the translocations the pairing of homologous regions leads to the unusual structure that contains four pairs of sister chromatids.
Nonreciprocal translocation (unbalanced)
Centromeric regions of two nonhomologous acrocentric chromosomes become fused to form single centromere.
-Down Syndrome chromosome 21 14 rearrangement leads to familial Down Syndrome. The heterozygote is normal the 3 chromosomes must separate during meiosis (only 2/6 are normal the rest either monosomic or trisomic) -Cancer (CML) type of leukemia translocation between chromosome 9 22 leads to the movement of a gene where it will be overexpressed 28 (No Transcript) 29 Fragile sites susceptible to breakage
Fragile X syndrome
Most common form of inherited mental retardation (1/4000 males 1/8000 females)
FMR1 gene has several trinucleotide repeats CGG in the 5UTR region
Normal individuals 6 to 54 repeats
Affected individuals gt230 repeats region becomes modified (bases are highly methylated gene NOT expressed)
Link between fragile sites cancer
Chromosome 3 FRA3B region FHIT gene often altered or missing in tumor cells taken from individuals w/ cancer
30 II. Chromosome Testing
High resolution chromosome analysis
31 A. karyotyping
adding a dye to metaphasic chromosomes different dyes that affect different areas of the chromosomes are used for a range of identification purposes.
Giemsa dye is effective because it markedly stains the bands on a chromosome Each chromosome can then be identified by its banding pattern
Chorionic Villi Biopsy
32 Prenatal genetic testing cont.
Maternal Serum Amniotic fluid
Unconjugated estriol (uE3)
Dimeric inhibin A (DIA)
Fetal cell sorting
33 B. High resolution chromosome analysis
SKY uses probes. Each of the individual probes complementary to a unique region of one chromosome - together all of the probes make up a collection of DNA that is complementary to all of the chromosomes within the human genome.
Each probe is labeled with a fluorescent color that is designated for a specific chromosome..
the probes hybridize the fluorescent probes essentially paint the full set of chromosomes can be analyzed to determine whether any of them exhibits translocations or other structural abnormalities.
34 (No Transcript) 35 2) In situ hybridization used to map specific deletions insertions No binding 13.1-13.3 deleted 36 (FISH) analysis of a normal individual (D) and patient with a chromosome 22 deletion using a probe for the UFD1 gene. The patient has only one copy of UFD1 seen in blue (white arrows). Chromosome 22 was labeled with a red fluorescent marker (yellow arrows). http//www.ggc.org/clinical.htm
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