Slide1: Chromosomal Inheritance, Sex Linkage, andamp; Sex Determination: Early 1900s Number of chromosomes generally is constant within species. Varies widely among species. Organism No. chromosomes Human 46 Chimpanzee 48 Dog 78 Horse 64 Chicken 78 Goldfish 94 Fruit fly 8 Mosquito 6 Nematode 11(m), 12(f) Horsetail 216 Sequoia 22 Tobacco 48 Cotton 52 Yeast 16


Slide2: 1902: Walter Sutton and Theodor Boveri Chromosome theory of inheritance: Independently recognized that the transmission of chromosomes from one generation to the next parallels inheritance of Mendelian factors. Mendelian factors (genes) are located on chromosomes. Support for theory derived from study of sex chromosomes.


Slide3: Sex chromosomes: Chromosomes or group of chromosomes in eukaryotes in which the sexes are represented differently. Typically designated X and Y (sometimes W and Z) Autosomes: All of the other chromosomes.


Slide4: Sex chromosomes in humans and Drosophila: Females XX Homogametic (one type of gamete, X) Males XY Heterogametic (two types of gametes, X or Y) Fig. 11.2: Pattern is same for: P x P andamp; F1 x F1


Slide5: Pattern is reversed in other species: Birds (Aves), butterflies (Insecta: Lepidoptera), and some fish (Pisces): Female WZ Male ZZ Plants - lots of different systems for sex determination. Drosophila uses X chromosome autobalance to determine sex. Other eukaryotes (e.g., yeast) use genic system - allele determines sex.


Slide6: Sex linkage: 1910: Thomas Hunt Morgan (Nobel Prize 1933) Experiments with Drosophila demonstrated chromosome theory of heredity. Discovered a mutant white-eyed male fly (wild type color is red). Next, crossed wild type female with white-eyed male. All F1 offspring had red eyes (therefore white is recessive). Crossed F1 x F1  F2 (3,470 red/782 white). All white-eyed flies also were male. Morgan hypothesized that eye color gene is located on the X chromosome. Ratio of white and red-eyed flies is 1/4.4 (observed) andlt;andlt; 1/3 (expected); white-eyed flies have lower viability.


Slide7: Fig. 11.3 Parental Cross F1 x F1


Slide8: Assuming eye color gene is located on the X chromosome: Males are hemizygous (w/Y) because there is no homologous gene on the Y chromosome. Females are either homozygous (w+/w+) or heterozygous (w+/w). F1 flies were w+/w (females) and w+/Y (males).


Slide9: Morgan’s hypothesis confirmed by reciprocal crosses: 100% Red 50%/50%


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Slide11:  F1 of red-eyed females and white-eyed males Morgan’s student Calvin Bridges: Discovered 1/2000 are either white-eyed female or red-eyed male. Hypothesized that X chromatids failed to separate in meiosis resulting in non-disjunction. Possible outcomes (aneuploidy = chromosomes absent or present in unusual number). YO  die (no X chromosome) XXX  die (extra X) Xw+O  red-eyed sterile males (no X from mother) XwXwY  white-eyed females (two X from mother)


Slide12: Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings. Fig. 11.5 Nondisjunction in meiosis involving the X chromosome


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Slide14: Fig. 11.8, Parallel behavior between Mendelian genes and chromosomes: Illustrates Mendel’s Principle of Independent Assortment


Slide15: Sex determination, 2 main mechanisms: Genotypic sex determination Y chromosome X chromosome Environmental sex determination e.g., Turtles use temperature andgt; 32°C produces females andlt; 28°C produces males


Slide16: 1. Genotypic sex determination Sex chromosomes play a decisive role in the inheritance and determination of sex. Two methods: Y chromosome mechanism (e.g., humans and other mammals) X chromosome-autosome balance system (e.g., Drosophila, Caenorhabditis nematode)


Slide17: Genotypic sex determination (cont.) Evidence for the Y chromosome mechanism: Y chromosome confers maleness and determines sex. Verified by studies of non-disjunction aneuploidy: XO 'Turner Syndrome' Female Sterile 1/10,000 (most XO fetuses die before birth). Survivors show below average height, poorly developed breasts, and immature sexual organs XXY 'Klinefelter Syndrome' Male 1/1000 Above average height, under-developed testes, and breast development in ~50% XYY-Male with above average height, fertility problems. XXX-Female, normal though sometimes less fertile.


Slide18: Genotypic sex determination (cont.) Dosage Compensation for X-linked Genes in Mammals: Two copies of X occur in females (XX), and one in males (XY). Gene expression must be equalized during development to avoid death. Different organisms use different dosage compensation systems.


Slide19: Genotypic sex determination (cont.) Dosage Compensation for X-linked Genes in Mammals: Female somatic cell nuclei contain a Barr body-a condensed, inactivated X chromosome. Most genes are inactivated but not all. Inactive X is randomly chosen in each cell at 16 days post-fertilization in humans. Descendants of each cell line have the same inactivated X, resulting in a mosaic. But different cell lines have different inactivated X. Results in mosaic color pattern seen in calico cats (X-linked genes for black and orange hair are inactivated randomly). Barr-body effect allows extra X chromosomes to be tolerated well (e.g., XXY possess 1 inactivated X; XXX possess 2 inactivated X, etc.). Regulated by specific loci, X inactivation center (Xic). Another gene, Xist, produces RNA that coats and silences the extra X. Barr bodies - easily visible under the light microscope. Autosomal duplications usually are lethal.


Slide20: http://www.mun.ca/biology/scarr/Barr_Bodies.jpg


Slide21: Genotypic sex determination (cont.) Gene for 'Maleness' on the Y chromosome: Gene(s) on the Y chromosome produce 'testis-determining factor'. Results in gonad differentiation during development. Other differences between sexes are secondary results of hormones and other factors produced by the gonads. Human SRY (sex-determining region Y) is believed to be the sex-determining gene that produces 'TDF'. Appears to be a transcription factor, regulating expression of other genes in the same region of the Y.


Slide22: Genotypic sex determination (cont.) X chromosome-autosome balance system - Drosophila: Y does not determine sex (XXY is female, XO is male). Sex is determined by the ratio of X chromosomes to autosomes (A). Normal female AA and XX 1:1 Normal male AA and XY 1:2 In contrast to mammals, X chromosome on male is up-regulated so that transcription level equals that of XX female. For aneuploid flies: Female X:A ≥ 1.0 Male X:A ≤ 0.5 Intersex 0.5 ≤ X:A ≤1.0 (sterile, mixed traits)


Slide23: Genotypic sex determination (cont.) X chromosome-autosome balance system - Caenorhabditis: Caenorhabditis elegans (nematode) also uses autosome balance. Two sexes, hermaphrodites (XX) and males (XO). Hermaphodite = possess both testes and ovaries. Dosage compensation limits transcription of each X on a hermaprhodite to 1/2 that of single X on male.


Slide24: Examples of X- andamp; Y-linked traits: Hemophilia X-linked recessive Occurs more frequently among males. Fathers transmit the recessive allele to all daughters and no sons. Webbed Toes X-linked dominant Hairy Ears Possibly Y-linked + autosomal gene(s), testosterone


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