Human karyotypeChromosome paintingX chromosomeAneuploidyB. DuplicationD. TranslocationTranslocation may not be reciprocalBiology 212 General Genetics Spring 2007Lectures 20 & 21: Human Genetics I & II: Chromosome DefectsReading: Text Chap. 5 to p. 168, pp. 174-189Lecture outline:1. Human karyotypes2. Sex chromosomes3. Variations in chromosome #4. Variations in chromosome structure5. PolyploidyLecture:1. Human karyotypesKaryotype: An array of all the chromosomes in a metaphase cell of an organism.Human karyotype46, XX female46, XY maleconsists of 22 pairs of autosomes, 1 pair of sex chromosomesPreparation of a karyotype: (see Fig. 5.2)1) Treat blood cells with colchicine to arrest dividing cells in metaphase2) Spread on a glass slide3) Stain with Giemsa4) Photograph5) Use computer to cut and paste chromosome images to create karyotypes6) Chromosomes arranged in pairs from largest (#1) to smallest (#22), followed by sex chromosomes XX or XYChromosome paintingUses fluorescently tagged DNA markers to identify each chromosome (see Fig. 5.1) by hybridizationAnatomy of a chromosometelomere shorter arm = p (petit)centromerelonger arm = q (queue: a long line)telomereRole of centromere1- Stabilize chromosome movement during cell division- Site where chromosome attaches to spindleAcentric chromosome: Chromosome that lacks a centromere; segregates abnormally in mitosis or meiosis.Dicentric chromosome: Chromosome with two centromeres; unstable, usually breaks during cell division.Centromere position in normal chromosomes can vary:Metacentric: centromere in middle of chromosomeSubmetacentric: centromere closer to one endAcrocentric: centromere near the end of the chromosome2. Sex chromosomesfemale 46, XXmale 46, XYX chromosome- female has twice the genetic material than males for genes on the X chromosome- dosage compensation: adjust for levels of gene expression- in humans and many organisms dosage compensation occurs by X-inactivation- the X-chromosome inactivated in each cell is randomly chosen- can observe inactive X chromosome as a Barr body in the cell nucleusY chromosome- Few genes are represented- Encodes SRY, master sex-determining gene- SRY encodes a transcription factor that is the testis determining factor- Transcription factors help determine the level of transcription of a gene- The pseudoautosomal region on the Y chromosome pairs with a region on the X- The Y chromosome is progressively shortening in mammalian evolution3. Variations in chromosome numberChromosome abnormalities occur in about 7.5% of all miscarriages.Types of common abnormalities (Table 5.1)Trisomy: one extra chromosome Monosomy: missing one chromosome 45, X (Turner syndrome) only viable human monosomyTranslocation: a chromosome rearrangement2Polyploid: extra set of chromosomesAneuploidy- Monosomy and trisomy are examples- Contains extra or missing chromosomes- Have an unbalanced chromosome set- Chromosomes behave unstably in cell divisionA common trisomy: Down syndrome = Trisomy 21- Affected individuals have 3 copies of chromosome 21- Affects 1/750 live birthsSymptoms:- Mental retardation- Short stature- Similar face shape- Shortened life span (<50 years)- Often have heart defects- Happy, responsiveMajor cause of Down syndrome:- Non-disjunction = improper chromosome segregation in meiosis I or meiosis II- Occurs more commonly in oogenesis- Likelihood of conceiving affected child mainly depends on age of mother (Fig. 5.12)Minor cause: hereditary form- Chromosome translocationSex chromosome abnormalitiesDue to non-disjunction in meiosis47, XXX female, mostly normal47, XYY male, tall, phenotypically mostly normal47, XXY male, Klinefelter syndrome, tall sterile, often mentally impaired45, XO female, Turner syndrome, short, sterile—doesn’t reach sexual maturity4. Variations in chromosome structure3A. Deletion or deficiencyA B C D E --> A B E- Missing a segment of the chromosome- Large mutations are usually lethalB. DuplicationA B C D E --> A B B C D E- Region of the chromosome is present twice- Produced by unequal crossing overC. InversionA B C D E --> A D C B E- A segment of the chromosome with the genes in reverse order- Inverted segment may include the centromere = pericentric inversion- OR inverted segment may be outside the region with the centromere = paracentricinversionD. TranslocationA B C D E --> A B Y ZX Y Z X C D E- Exchange of parts between non-homologous chromosomes- Reciprocal translocation (balanced translocation) is swapping the ends of the chromosomes- Translocation may not be reciprocalIndividuals with chromosome defects have high risk of errors in meiosisRefer to practice problems that look at pairing of chromosomes in heterozygotes5. Polyploidy = extra full set of chromosomes- lethal in humans- common in plants to have extra chromosome setshaploid = chromosome set in a gametediploid = chromosome set in most eukaryotic cells = 2 monoploid setstriploid = 3 monoploid sets4tetraploid = 4 monoploid sets- In evolution of plants it is common for hybridization of gametes to occur from different but related species to produce a new polyploid species- In agriculture, polyploids often produce larger flowers and or larger or more desirable fruit.- A few other organisms are also polyploid: trout are