Changes in chromosome number Changes in whole sets of chromosomes changes in ploidy Reading Hartwell pp516 525 Problem set at end Changes in of individual chromosomes aneuploidy Some definitions Ploidy is the of sets of chromosomes Monoploids x is the number of chromosomes in a set Haploid n is the number of chromosomes in a gamete For diploids x n But in polyploids where the ploidy is 2x n x Male bees and wasps are naturally occuring monoploids which develop by parthenogenesis Can also generate experimentally e g zebrafish many plants e g wheat is a hexaploid or 6x where x 7 and n 21 Zebrafish geneticists take advantage of monoploids in genetic screens In plants can generate monoploids by culturing meiotic products Need to be studying a phenotype that you can see during embryogenesis before monoploids die 1 BUT sterile In meiosis no pairing homologs All gametes abnormal Only 2 gametes OK With increasing x of functional gametes decreases Tetraploids 4x hexaploids 6x octaploids 8x Can artificially use colchicine to increase ploidy Increasing ploidy increasing size 2n 8n Triploids are sterile Generated by crossing diploid and tetraploid 2x x 4x 3x Bananas seedless watermelons are seedless because they are triploid 2 But why are they sterile 2 gametes 2x OK 2 gametes 1x OK 2 gametes unbalanced Up until now we have been dealing with autopolyploids which contain multiple sets of chromosomes from the same species Allopolyploids are produced from sets of chromosomes of closely related species 2 gametes unbalanced Closely related chromosomes from different species are not homolgous but are referred to as homeologous Homeologous chromosomes do not pair during meiosis and this can lead to problems If cross two related species ok until meiosis Homeologous chromosomes don t pair which leads to sterility One successful allopolyploid is Triticale Triticum wheat Fertile Triticale 6n 42 8n 56 Gametes 3n 21 Sterile hybrid But by doubling the chromosomes generate an allopolyploid amphidiploid that is fertile Secale Rye 2n 14 gametes n 7 4n 28 Chromosome doubling with colchicine Triticale combines the high protein content of wheat with the high lysine levels and ability to adapt to marginal environments of rye Amniocentesis Aneuploidy 3 Chromosomes can be identified by their size and banding pattern Normal female XX Normal male XY Meiosis results in gametes with a single set of chromosomes Nondisjunction in meiosis I or II results in gametes with an extra or missing chromosome When these gametes fuse the fusion results in zygotes with an extra or missing chromosome a situation termed aneuploidy What are the consequences of aneuploidy in humans 4 Autosomes first All monosomic 43 autosomes missing an autosome spontaneously abort miscarriage Almost all trisomic 45 autosomes an extra autosome fetuses spontaneously abort There are exceptions Trisomy 13 Patau Syndrome Trisomy 18 Edwards Syndrome Trisomy 21 Down Syndrome Can survive to age 50 Mental retardation Many fetuses spontaneously abort Those that make it die in first year But why do aneuploid fetuses die 1000s of genes are over or under expressed Resulting in genetic imbalance the consequences of genetic imbalance are different in plants and animals 5 Turner syndrome XO But the rules are different for the sex chromosomes Female Short wide chested Underdeveloped breasts Rudimentary ovaries Sterile Normal intelligence Klinefelter syndrome XXY ALL autosomal monosomics die BUT XO individuals often survive and can be relatively normal There is something different about the autosomes and sex chromosomes The Y chromosome is necessary and sufficient for male development But what on Y is important for male development Male Phenotype of syndrome not apparent until puberty Breast development Low fertility Subnormal intelligence SRY is both necessary and sufficient for male development The mouse on the left is XY and the mouse on the right is XX and has an SRY transgene both are phenotypic males 6 Yet another difference between sex chromosomes and autosomes Autosomal trisomies die but XXY XYY and XXX trisomies survive BUT WHY One of the first clues came from Liane Russell Additional results Mice heterozygous for a recessive coat color mutation c on an autosome had wild type dark fur homozygotes have white fur c X chromosomes autosome But a strain carrying a reciprocal translocation more on these later between X and the autosome was variegated having patches of wild type and mutant fur In other words having the c wild type coat color gene fused to X resulted in a mutant phenotype in some tissues X linked mutations sometimes result in variegated phenotype in females Females that are heterozygous for a mutant version of the glucose 6 phosphate dehydrogenase gene that lacks activity and produces an electrophoretic variant were analyzed When tissue from these individuals was analyzed it possessed activity and contained both isoforms If isolated cells were cultured and then examined the clones either had G 6 PD activity or lacked it expressing only a single isoform Murray Barr noted that the nuclei of female but not male cats contained a darkly stained element This is now known as a Barr body XX XXX One Barr body Two Barr bodies 7 Karyotype XY XO XX XXX Barr bodies 0 0 1 2 In mammalian females early in embryonic development each cell inactivates one X chromosome In 1961 Mary Lyon proposed that in mammals the dose of gene products was equalized between males and females by inactivating one of the X chromosomes in females The inactive X is the Barr body This mechanism of dosage compensation is often referred to as the Lyon hypothesis Whoa All mammalian females are mosaic These cells express only paternal X chromosome genes These cells express only maternal X chromosome genes X inactivation results in black and orange patches on Calico cats orange gene black gene Female Calico cats have black and orange alleles of an X linked gene These cells express only paternal black gene These cells express only maternal orange gene 8 Certain X linked inherited traits result in mosaicism in females e g anhidrotic ectodermal dysplasia But how is only one X inactivated Studies of X autosome translocations defined a specific site on X known as the X inactivation center Xic that was required for inactivation The Xic contains a gene that encodes and RNA with no protein coding capacity Xist Xist RNA coats the inactive X Xic X chromosome autosome chromosome can be inactivated
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