5 Human Karyotypes and Chromosome Behavior. Human Chromosomes Humans contain 46 chromosomes,...
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Transcript of 5 Human Karyotypes and Chromosome Behavior. Human Chromosomes Humans contain 46 chromosomes,...
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
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
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
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
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
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
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
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
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
Chromosome Deletions
• Deletions = missing chromosome segment• Polytene chromosomes of Drosophila can be
used to map physically the locations of deletions
• Testcross mapping shows which wild-type alleles are lost by deletion
• Large deletions are often lethal
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
Red-Green Color Vision Genes
• Green-pigment genes 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
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
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
Chromosome Inversions
• Crossing-over within a pericentric inversion loop during homologous recombination results in duplications and deletions of genetic information
• Deletions and duplications occur because inversion loop causes misalignment of chromosomes during homologous pairing = synapsis
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
Reciprocal Translocation
• Heterozygous translocation = only one pair of non-homologous chromosomes is affected
• Homozygous translocation = both pairs of non-homologous chromosomes are affected
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
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
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
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
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
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
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
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
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