Human Karyotypes and Chromosome Behavior 5 Human Karyotypes and Chromosome Behavior

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