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Chromosome Theory of Inheritance

Chromosome Theory of Inheritance. 1902 Sutton and Boveri A chromosome is a linkage group of Mendelian factors (GENES) How many linkage groups in the human species? 1920s Morgan et al. Genes are in a linear sequence on the chromosomes, they can be mapped. Chromosomes in most animals.

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Chromosome Theory of Inheritance

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  1. Chromosome Theory of Inheritance • 1902 Sutton and Boveri • A chromosome is a linkage group of Mendelian factors (GENES) • How many linkage groups in the human species? • 1920s Morgan et al. • Genes are in a linear sequence on the chromosomes, they can be mapped

  2. Chromosomes in most animals • pairs of autosomes • 1 pair sex chromosomes • XY heterogametic • XX homogametic Human karyotype ->

  3. Do more chromosomes mean more intelligence? Human 46 Chimpanzee 48 Dog 78 Cat 72 Alligator 32 Goldfish 94 Mosquito 6 Potato 48 Baker’s yeast 34

  4. I. Mammalian sex determination = the Y system A. Embryo is neither male nor female Week 7 How does embryo “know to become male?

  5. XY embryo sex chromosomes • The Y determines sex…. XY = male XX = female

  6. B. SRY gene encodes TDF (Testes determining factor, 1990) • SRY (sex determining region Y) • Short arm (p) • TDF is a 20 aa protein (a transcription factor) • TDF stimulates the growth of testes --> • testosterone ---> sperm ducts, male brain “sensitization”

  7. XX males: If SRY crosses over to the X chromosome during meiosis (formation of sperm) Father during meiosis X from father + X from mother

  8. A 17 year old female presented with “streak” ovaries, no uterus, no menstrual cycle • XY female • Embryo has Y chromosome but does not develop as male • Mutation in SRY  ?

  9. II. Other sex determination systems A. Drosophila Ratio of X to sets of autosomes • embryo “calculates” ratio X/A = 1 or >1 ------> female X/A = 0.5 or <0.5 --------> male X/A between 0.5 and 1 ---> intersex

  10. What is the sex of an XY fly with 2 sets of autosomes? • What is the sex of a fly with with 2 sets of autosomes but 1 X chromosome • What is the sex of a triploid fly with 2 X chromosomes?

  11. B. ZW system - birds PCR analysis of sex chromosomes • Females are ZW (heterogametic) • Males are ZZ (homogametic)

  12. C.Temperature sex determination (TSD) • In some reptiles sex is not determined genetically! (Varies widely) • majority of endangered reptiles use TSD - sea turtles, Galapagos tortoises, alligators, crocodiles

  13. Parthenogenesis – eggs develop without sperm (asexual) Komodo dragon Parthenogenesis ZW system, all offspring of parthenogenesis are male Why?

  14. IV. Dosage Compensation (mammals) • Females have 2 Xs, males have 1 X. Do females have an extra dose of X-linked genes/alleles?

  15. X chromosome inactivation Lyon, 1961 • Observe dense “Barr body” at edge of nucleus in female cells • Heterochromatic (stains darker) Male cell female cell cell with 2 Barr bodies Number of X chromosomes?

  16. Random X-inactivation, mechanism ~1000 cell embryo • random inactivation of X • XIC, Xist gene on X chromosome • transcribed 24 hours prior to inactivation • mRNA “cages” X-chromosome • caged X becomes a Barr body XIC X X

  17. Which X is inactivated appears to be random Barr body mRNA Embryo develops patches

  18. Female mosaics • All females heterozygous for X-linked traits are mosaics for those traits. red/green colorblindness XCXc phenotype = ? Look at retina of heterozygous female

  19. Anhydrotic ectodermal dysplasiaXAXa females XaY males Tooth + nail abnormalities, life threatening hyperthermia, sparse hair

  20. Similarities and differences X and Y • Most genes on Y are for development and fertility • (Human has ~80 Y genes) • (Kangaroo has only SRY on the Y) ~ 80 genes

  21. Pseudoautosomal region of the X and Y • ~12 genes on X and Y • regions allow X and Y to pair during meiosis • pseudoautosomal genes are also transcribed from the inactivated X! • both males and females have 2 active copies of these genes

  22. Chromosomal Abnormalities KARYOTYPE 1. Obtain white blood cells from or fetal cells from amniotic fluid 2. Proliferation via growth factor add colchicine at metaphase to arrest spindle formation 3. add water to swell cell -> squash 4. stain ->photograph Detects number of chromosomes, sex, chromosomal abnormalities

  23. Amniocentesis usually done week 14 Karyotype and analyze fluid for enzyme defects

  24. Chorionic villus sample (CVS) usually done week 8 More risk, but earlier results

  25. Arrange in pairs according to: • decreasing size • centromere position • banding pattern METACENTRIC SUBMETACENTRIC ACROCENTRIC

  26. metacentric (1) submetacentric (9) p arm is the upper, shorter arm

  27. Normalmale 46, XY Which are meta-, submeta- acrocentric?

  28. Aneuploidy (versus euploidy) • Trisomy (not triploid) • 47, 21+ (1/800 live births) 21 may be small, but contains 33,546,361 bp of DNA!

  29. Down Syndrome (J. Langdon H. Down, 1866) effects • Developmental delays • Possible heart defects, hearing loss, hypotonia, thyroid problems, obesity • Epicanthic eye folds • Wide tongues • Greater risk of Alzheimer’s

  30. Trisomy 13 (Patau) • Fatal< 1 year (usually) • Deaf, blind, clyclopia, polydactly, cleft palate • 1/5000 live births 47, XY, 13+

  31. 47, XY, 18+ (Edward’s) • < few months1/5000 live births

  32. Human trisomies of the sex chromosomes (see pg 293) • 47, XXY = Klinefelter’s • 47, XXX • 47, XYY

  33. Monosomy (only 1 viable in humans!) • 45 X, • Turner Syndrome (1/2000 live births) • Partial monosomy 46, 5p- • Cri du Chat • Arises due to a deletion on the short arm of chromosome 5

  34. Cri du Chat 46, 5p-1/50,000 live births • pseudodominance for deleted region • Microcephaly, myotonia, “cry of cat”, retardation • if individuals make it past childhood, symptoms lessen

  35. Polyploidy = extra SETS of chromosomes • # in humans • Triploid, tetraploid • Octoploid etc..

  36. Many plants are polyploid • Some bees and wasps are monoploid

  37. In humans Monosomy Trisomy Tetrasomy

  38. Deletions (del) • can observe large ones by karyotype • If centromere is lost, then chromosome will be lost • Heat, chemicals, radiation • Unequal crossing over during meiosis

  39. 46,XX,del(7)(q21.12,q21.2) • Pseudodominance • Lethal if both chromosomes Leads to problems during meiosis

  40. Duplications • segment of a chromosome doubles • May be tandem or reverse • problems during meiosis

  41. dup(5)(qter->q33.1::p15.3->qter) • Sample of cord blood from stillborn male with anencephaly

  42. Inversions (inv) • 180o turnaround of segment • no loss of genetic material • may change length ratio of p/q arms • Position effect • change in gene position with respect to centromere • being near heterochromatic region may influence expression

  43. Translocations- segment moves to other chromosome - interstitial or reciprocal exchange • t (13;14) • Individual has all genetic material, but what about gametes?

  44. t(11;13) (q21;q14.3) • the parent who has the translocation is phenotypically normal as all genetic info is present • The gametes, however, are not as evidence by multiple miscarriages

  45. Translocation (cont.) • Robertsonian fusion • ends of 2 acro- or telocentric break/fuse • 45 chromosomes but no, or little, loss of genetic material

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