Human Karyotypes and Chromosome Behavior

1. 5 Human Karyotypes and Chromosome Behavior

2. Human Chromosomes • Humans contain 46 chromosomes, including 22 pairs of homologous chromosomes and two sex chromosomes • Karyotype = stained and photographed preparation of metaphase chromosomes arranged in homologous pairs in descending size order

4. Human Chromosomes • Chromosome maps are prepared by dividing the chromosome into two regions (arms) separated by the centromere • p = short arm (petit); q = long arm • p and q arms are divided into numbered bands and interband regions based on pattern of staining

5. Centromeres Centromeres may be located in different regions of a chromosome: • Metacentric = located in middle of chromosome • Submetacentric= located closer to one end of chromosome • Acrocentric = located near one end of chromosome

7. Human X Chromosome • Females=2 copies of X chromosome • One copy of X is randomly inactivated in all somatic cells • Females are genetic mosaics for genes on the X chromosome; only one X allele is active in each cell • Barr body = inactive X chromosome • Dosage Compensation=dosage equalization for active genes

9. Human Y Chromosome • Y chromosome is largely heterochromatic (condensed inactive chromatin) • Important regions of Y chromosome: -pseudoautosomal region=region of shared X-Y homology -SRY=master sex controller gene which encodes testis determining factor (TDF) for male development

10. Abnormal Chromosome Number • Euploid=balanced chromosome abnormality=equal number of copies • aneuploid=unbalanced set of chromosomes=unequal copy number • monosomic=loss of a single chromosome copy

11. Abnormal Chromosome Number • Trisomy of chromosome 21 = most common autosomal (non-sex chromosome) aneuploidy • Down Syndrome = genetic disorder due to trisomy 21 = aneuploidy • Amniocentesis=fetal cells are analyzed for abnormalties of chromosome number and structure

12. Extra or Missing Chromosomes • Polysomy= extra copies of single chromosomes in a cell • Trisomy = extra copy of chromosome • Trivalent = abnormal pairing of trisomic chromosomes in cell division • Univalent = extra chromosome in trisomy is unpaired in cell division

14. Sex Chromosome Aneuploidies • trisomy-X=47, XXX (female) • double-Y=47, XYY (male) • Klinefelter Syndrome=47, XXY (male, sterile) • Turner Syndrome=45, X (female, sterile) • Fragile-X syndrome= X chromosome instability resulting from high copy number of trinucleotide repeat

15. Chromosome Deletions • Deletions = missing chromosome segment • Polytene chromosomes of Drosophila can be used to map physically the locations of deletions • Testcross mappingshows which wild-type alleles are lost by deletion • Large deletions are often lethal

17. Gene Duplications • Duplication= chromosome segment present in multiple copies • Tandem duplications= repeated segments are adjacent • Tandem duplications often result from unequal crossing-over due to mispairing of homologous chromosomes during meiotic recombi-nation

19. Red-Green Color Vision Genes • Green-pigmentgenes may be present in multiple copies on the X-chromosome due to mispairing and unequal crossing-over • Unequal crossing-over between these genes during meiotic recombination can also result in gene deletion and color-blindness • Results in chimeric (composite) gene

20. Chromosome Inversions • Inversions = genetic rearrangements in which the order of genes is reversed in a chromosome segment • Inversions do not alter the genetic content but change the linear sequence of genetic information • At synapsis = homologous pairing, inversion loops form

22. Chromosome Inversions • Paracentric inversion = does not include centromere; Pericentric inversion = includes centromere • Crossing-over within a paracentric inversion loop during recombination produces one acentric (no centromere) and one dicentric(two centromeres) chromosome

24. Chromosome Inversions • Crossing-overwithin a pericentric inversion loopduring homologous recombination results in duplications and deletions of genetic information • Deletionsand duplicationsoccur because inversion loop causes misalignment of chromosomes during homologous pairing = synapsis

26. Reciprocal Translocations • Reciprocal translocations = exchange of genetic segments between non-homologous(unrelated) chromosomes • There is no loss of genetic information but the functions of specific genes may be altered • Reciprocal translocation may affect one or both pairs of chromosomes

27. Reciprocal Translocation • Heterozygous translocation = only one pair of non-homologous chromosomes is affected • Homozygoustranslocation = both pairs of non-homologous chromosomes are affected

29. Reciprocal Translocations • Synapsis involving heterozygous reciprocal translocation results in pairing of four pairs of sister chromatids = quadrivalent • Chromosome pairs may segregate in several ways during meiosis, with varying genetic outcomes in gametes

30. Reciprocal Translocation 3 outcomes of meiotic segregation: • Adjacent-1 segregation: homologous centromeres separate at anaphase I; gametes contain duplications and deletions • Adjacent-2 segregation: homologous centromeres stay together at anaphase I; gametes have a segment duplication and deletion

31. Reciprocal Translocation • Alternate Segregation: half the gametes receive both parts of the reciprocal translocation and the other half receive both normal chromosomes; all gametes are euploid = normal genetic content, but half are translocation carriers

32. Robertsonian Translocation • Robertsonian translocation = fusion of two acrocentric chromosomes in the centromere region • Translocation results in apparent loss of one chromosome in karyotype analysis • Genetic information is lost in the tips of the translocated acrocentric chromosomes

34. Robertsonian Translocation Meiotic segregation (14:21): • Adjacent-1 segregation: 1/2 gametes have extra copy of most of chromosome 21 (fertilization will produce Down Syndrome = trisomy 21); 1/2 gametes have no copy of 21 • Adjacent-2 segregation: 1/2 gametes contain duplications; 1/2 lack chromosome 14

35. Robertsonian Translocation • Alternate Segregation: all gametes are euploid; 1/2 are carriers of the Robertsonian translocation • Translocations may produce position effects = changes in gene function due to repositioning of gene • Gene expression = elevated or decreased in translocated gene

36. Polyploidy • Polyploidy = genome composed of multiple complete sets of chromosomes; occurs in plants • Haploid = set of unpaired chromosomes found in gametes • Diploid = set of paired homologous chromosomes found in most cells; total number is fixed for a species

38. Chromosome Number • monoploid= basic set of chromosomes; number fixed for species • diploid = 2 copies of monoploid set • triploid= 3 copies of monoploid set • tetraploid= 4 copies of monoploid set • hexaploid= 6 copies of monoploid set

39. Endoreduplication • Endoreduplication=doubling of the chromosome complement • Tetraploidy=chromosomes fail to segregate during meiosis or mitosis • autopolyploidy=chromosomes derived from single diploid • Chromosome painting = chromosomes hybridized with fluorescent dye to show origins