Genetic Variation.pdf

Genetic Variation Genetic Variation Genetic Variation ▪ The value of meiosis - Meiosis introduces genetic ▪ Genetic variation refers to the differences variation in DNA sequence...

Genetic Variation Genetic Variation Genetic Variation ▪ The value of meiosis - Meiosis introduces genetic ▪ Genetic variation refers to the differences variation in DNA sequences among individuals within - gametes of offspring do not have a population or between populations of the same genes as gametes from h same species. parents ▪ genetic recombination Sources of Genetic Variation h ▪ Mutations - Changes in the DNA sequence that can introduce new genetic variations. s ▪ Genetic Recombination - During sexual reproduction, the mixing of parental genes creates new combinations of alleles. ▪ Crossing over - creates completely new e ▪ Gene Flow -The movement of genes combinations of traits iin next between populations, often through generation migration, which introduces new genetic material Genetic Variation ▪ Meiosis and Crossing over introduce great genetic variation to population ❑ drives evolution ▪ Random fertilization ▪ Source of Genetic Variability Parts of Chromosomes 1. Centromere structure in a chromosome that holds together the two chromatids centromere is the point of attachment of h the kinetochore, a structure to which the microtubules of the mitotic spindle become anchored. h 2. Kinetochores sites where the spindle fibers attach. es 3. Telomere a region of repetitive nucleotide sequences at each end of a chromatid, protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes Genetic Variation ▪ Structure of the Chromosome ▪ Classification of Chromosome ▪ Karyotyping ▪ Chromosome Abnormalities Number Structure 4. Satellite ▪ Acrocentric Bulge on the telomeric end A chromosome whose centromere is Satellites of chromosomes have repetitive, placed very close to, but not at, one end heterochromatic DNA sequences. During the replication of the chromosomes Human Chromosomes the ends of chromosomal sequences are truncated. ▪ Replicated chromosomes at metaphase h As the satellites are nonsense sequences consist of sister chromatids joined by a they are lost during replication thus single centromere protecting the useful euchromatic DNA towards the core of the chromosome. sh Metaphase Chromosomes e ▪ Chromosomes are identified by size, centromere location, banding pattern Chromosome Number ▪ Chromosome number in selected organisms Types of Chromosomes ▪ Sex chromosomes In humans, the X and Y chromosomes that are involved in sex determination. These Centromere Location have different sizes and shapes ▪ Metacentric ▪ Autosomes A chromosome that has a centrally placed Chromosomes other than the sex centromere chromosomes In humans, chromosomes 1 to 22 are ▪ Submetacentric autosomes A chromosome whose centromere is placed closer to one end than the other A Set of Human Chromosomes Karyogram: Chromosome Banding Patterns ▪ Human chromosomes are analyzed by construction of karyotypes ▪ Karyotype A complete set of chromosomes from a h cell that has been photographed during cell division at the metaphase stage and arranged in a standard sequence h Chromosomes ▪ 22 autosomes and sex chromosomes in pairs ▪ Classified according to: s Length position of centromere presence or absence of satellites ▪ Chromosomes divided into groups labelled e A-G –A 1-3 ISCN –B 4-5 ▪ International System for Human –C 6-12 + X Cytogenetic Nomenclature –D 13-15 ▪ Each area of chromosome given –E 16-18 number –F 19-20 ▪ Lowest number closest –G 21-22 +Y (proximal) to centromere ▪ Highest number at tips (distal) to 1. Karyotyping centromere A laboratory test used to study an individual's chromosome make-up. ISCN 2. Karyotype ▪ del - deletion photomicrographs wherein chromosomes ▪ dic - dicentric are arranged in homologous pairs, and in ▪ fra - fragile site descending order of size and relative ▪ i - isochromosome position of the centromere. ▪ inv - inversion ▪ p - short arm ▪ r - ring ▪ der - derivative ▪ dup - duplication ▪ h - heterochromatin ▪ ins - insertion ▪ mat - maternal origin ▪ q - long arm ▪ t - translocation , 46,XX,del(5p) ▪ separates chromosome numbers sex chromosomes chromosome abnormalities ; h 46,XX,t(2;4)(q21;q21) ▪ separates altered chromosomes h break points in structural rearrangements involving more than 1 chromosome ▪ Normal male s 46,XY ▪ Normal female 46,XX Metaphase Chromosomes (a) e Arranged Into a Karyotype (b) System of Naming Chromosome Bands ▪ Allows any region to be identified by a descriptive address (chromosome number, arm, region, and band) Constructing and Analyzing Karyotypes ▪ Karyotype construction and analysis are used to identify chromosome abnormalities Karyotyping – cell preparation ▪ Different stains and dyes produce banding patterns specific to each chromosome ▪ Need metaphases ▪ Karyotypes reveal variations in ▪ Culture cells until sufficient mitotic activity chromosomal structure and number ▪ Add colchicine (or colcemid) to arrest in 1959: Discovery that Down syndrome is metaphase caused by an extra copy of chromosome 21 prevents mitotic spindle fibres forming ▪ Chromosome banding and other ▪ Add hypotonic salt solution to swell cells techniques can identify small changes in ▪ Fix with mix of methanol;acetic acid chromosomal structure ▪ Want long chromosomes with none overlapping Information Obtained from a Karyotype Obtaining Cells for Chromosome Studies ▪ Any nucleus can be used to make ▪ Number of chromosomes karyotype ▪ Sex chromosome content Lymphocytes, skin cells, cells from ▪ Presence or absence of individual biopsies, tumor cells chromosomes ▪ Nature and extent of large structural ▪ Sampling cells before birth h abnormalities Amniocentesis Chorionic villus sampling (CVS) Karyotyping ▪ Staining methods to identify chromosomes Amniocentesis h ▪ G banding - Giemsa ▪ A method of sampling the fluid surrounding ▪ Q banding - Quinacrine the developing fetus by inserting a hollow ▪ R banding - Reverse needle and withdrawing suspended fetal s ▪ C banding - Centromeric cells and fluid (heterochromatin) Used in diagnosing fetal genetic and developmental disorders ▪ Ag-NOR stain - Nucleolar Organizing Usually performed in the sixteenth week of e Regions (active) pregnancy Chromosomal Aberrations and Specific Syndromes Chromosome Painting ▪ New techniques using fluorescent dyes generate unique patterns for each chromosome Chorionic Villus Sampling (CVS) Polyploidy Changes the Number of Chromosome Sets ▪ A method of sampling fetal chorionic cells by inserting a catheter through the vagina or ▪ Triploidy abdominal wall into the uterus A chromosomal number that is three times Used in diagnosing biochemical and the haploid number, having three copies of cytogenetic defects in the embryo all autosomes and three sex chromosomes h Usually performed in the eighth or ninth week of pregnancy ▪ Tetraploidy A chromosomal number that is four times the haploid number, having four copies of all h autosomes and four sex chromosomes A Triploid Karyotype es Variations in Chromosome Number ▪ Changes in chromosome number or chromosome structure can cause genetic Keep In Mind disorders ▪ Polyploidy results when there are more than two complete sets of chromosomes ▪ Two major types of chromosomal changes can be detected in a karyotype Aneuploidy Involves the Gain or Loss of A change in chromosomal number Individual Chromosomes A change in chromosomal arrangement ▪ Monosomy Changes in Chromosome Number A condition in which one member of a chromosomal pair is missing; one less than ▪ Polyploidy the diploid number (2n – 1) A chromosomal number that is a multiple (3n or 4n) of the normal haploid ▪ Trisomy chromosomal number A condition in which one chromosome is present in three copies, and all others are ▪ Aneuploidy diploid; one more than the diploid number A chromosomal number that is not an (2n + 1) exact multiple of the haploid number Causes of Aneuploidy Trisomy 13: Patau Syndrome (47,+13) ▪ Nondisjunction The failure of homologous chromosomes ▪ A lethal condition to separate properly during meiosis ▪ 1 in 10,000 births, most die within 1st month Nondisjunction in Meiosis I Leads to - Usually have polydactyly, eye Aneuploidy defects, severe brain, nervous h system & heart defects Trisomy 21: Down Syndrome (47, +21) ▪ Occurs in 1/800 births h ▪ Trisomy 21 is the only autosomal trisomy that allows survival into adulthood ▪ Mental retardation ▪ Characterized by epicanthic fold (corner of s eye) ▪ large furrowed tongues ▪ 40% have congenital heart defects High risk of leukemia & Alzheimer’s e disease Few reach the age of 50 Trisomy 21: Down Syndrome (47,+21) - Monosomy and trisomy involve the loss and gain of a single chromosome to a diploid genome Effects of Monosomy and Trisomy What Are the Risks for Autosomal Trisomy? ▪ Autosomal monosomy is a lethal ▪ The causes of autosomal trisomy are condition unknown Eliminated early in development ▪ Factors that have been proposed include: (spontaneous abortion) Genetic predisposition ▪ Some autosomal trisomies are Exposure to radiation relatively common Viral infection Most result in spontaneous abortion Abnormal hormone levels Three types can result in live births (13, ▪ Maternal age is the leading risk factor for 18, 21) trisomy - 94% of nondisjunctions occur in the mother Trisomy 18: Edwards Syndrome (47,+18) Why is Maternal Age a Risk Factor? ▪ A lethal condition Survival only 2-4 mths ▪ 1 in 11,000 births ▪ Meiosis is not completed until ovulation ▪ 80% are females - Intracellular events may increase ▪ Very slow growth, Mental retardation, risk of nondisjunction, resulting in Heart malformations aneuploidy ▪ Maternal selection Structural Alterations Within - Embryo-uterine interactions that Chromosomes normally abort abnormal embryos become less effective ▪ Changes in the structure of chromosomes - Age of the mother is the best known Deletion risk factor for trisomy Duplication Translocation h Aneuploidy of the Sex Chromosomes Inversion ▪ More common than autosomal aneuploidy ▪ Can involve both X and Y chromosomes h ▪ A balance is needed for normal development - At least one copy of the X Deletions s chromosome is required for development ▪ Deletions involve loss of chromosomal - Increasing numbers of X or Y material chromosomes causes progressively ▪ Deletions of chromosomal segments are e greater disturbances in phenotype associated with several genetic disorders and behavior Cri du chat syndrome Prader-Willi syndrome Turner Syndrome (45,X) ▪ Monosomy of the X chromosome that results in female sterility. Other phenotypic characteristics but otherwise normal. Klinefelter Syndrome (47, XXY) Deletion in Chromosome 5 and cri du ▪ Individuals (males) have some fertility chat syndrome problems but few additional symptoms Associated with an array of malformations, the most characteristic of which is an infant XYY Syndrome (47,XYY) cry that resembles a meowing cat due to defects in the larynx ▪ Affected individuals are usually taller than By comparing the region deleted with its normal and some, but not all, have associated phenotype, investigators have personality disorders identified regions of the chromosome that carry genes involved in developing the Changes in the number of sex larynx. chromosomes have less impact than changes in autosomes Translocations ▪ Aneuploidy also is associated with many cancers ▪ Translocation involves exchange of chromosome parts Chromosomal Abnormalities - Often produces no overt phenotypic in Miscarriages effects - Can result in genetically imbalanced h and aneuploid gametes ▪ Chromosomes can lose, gain, or rearrange segments h Robertsonian Translocation ▪ A translocation resulting in Down syndrome s - Robertsonian translocation makes Down syndrome a heritable genetic disease - Potentially present in one in three e offspring Robertsonian Translocation and Down Syndrome What Are Some Consequences of Aneuploidy? ▪ Aneuploidy is the leading cause of reproductive failure in humans - Results in miscarriages and birth defects