CHAPTER 5 Human Chromosomes and Chromosome Behavior Generally speaking animals are much less tolerant of chromosomal changes than are plants 5 1 Human beings have 46 chromosomes in 23 pairs Chromosomes are labeled via chromosome painting where different colors are painted on each chromosome by hybridization formation of duplex molecules with different dyes The standard human karyotype consists of 22 pairs of autosomes and two sex chromosomes Chromosomes can also be treated with a staining reagent called Giemsa causing chromosomes to exhibit transverse bands G bands form where there is low abundance of G C base pairs Chromosomes grouped into seven sets A G basted on size and centromere position X C Y G Gene density is NOT highly correlated with chromosome size Chromosomes with no centromere or with two centromeres are genetically unstable A chromosome with its centromere about in the middle is a metacentric chromosome arms are of equal length and each daughter forms a V shape at anaphase When the chromosome is somewhat off center the chromosome is a submetacentric chromosome and each daughter forms a J shape at anaphase A chromosome with the centromere very close to one end appears I shaped at anaphase arms are unequal in length and it is an acrocentric chromosome A chromosome that lacks a centromere is an acentric chromosome which is genetically unstable chromosomes with two centromeres are dicentric chromosomes Dosage compensation adjusts the activity of x linked genes in females Dosage compensation is where the unequal dosage in the sexes is corrected either by increasing the activity of genes in the X chromosome in males or by reducing the activity of genes in the X chromosome in females X inactivation occurs roughly when the embryo has 64 128 cells 15 escape inactivation This accounts for differences in traits expression between males and females and phenotypic variation among individuals with abnormal numbers of X chromosomes One consequence of X inactivation is it results in dosage compensation a concept originally proposed by Mary Lyon called the single active X principle Another consequence of X inactivation is a normal female is a mosaic or contains cells of two or more different genotypes for the expression of x linked genes Ex Sweat glands in females The calico cat shows visible evidence of x chromosome inactivation orange and black patches Some genes in the X chromosome are also present in the Y chromosome Regions of homology enable the X and Y chromosomes to synapse in spermatogenesis and a crossover takes place that holds the chromosomes together to ensure proper segregation These regions of shared X Y homology define the pseudoautosomal regions Rate of recombination per nucleotide pair is at least 20x greater in the PARp than in autosomes Because of recombination in the pseudoautosomal region a mutant allele in this region is neither completely X or Y linked but can move back and forth between chromosomes A gene that shows an autosome like pattern of inheritance but is known to reside in a pseudoautosomal region is said to show pseudoautosomal inheritance The pseudoautosomal region of the X and Y chromosome has gotten progressively shorter in evolutionary time X and Y chromosomes started out as autosomes and diverged 300 350 mya Y chromosome includes genes that encode about 26 distinct proteins many of which are important for male fertility many repeats which undergo genes conversion The gene SRY master sex determining gene codes for a protein transcription factor the testis determining factor TDF SRY evolution Y chromosome diverges X Y recomb in telomeres The history of human populations can be traced through studies of the Y chromosome The set of alleles at two or more loci present in a particular chromosome is a haplotype Y chromosomes with haplotypes that share alleles at each of 20 30 SSRs across the chromosome must have descended from the same ancestral Y chromosome in the very recent past 5 2 Chromosome abnormalities are frequent in spontaneous abortions 15 of pregnancies terminate in spontaneous abortion and have chromosome abnormalities Many spontaneously aborted fetuses have trisomy of one of the autosomes Triploid and tetraploid are examples of euploid conditions same relative gene dosage Trisomy creates unbalanced chromosome complements aneuploid Euploid abnormalities generally have less severe phenotypic effects than aneuploid abnormalities When a diploid organism has a missing copy of a chromosome the condition is monosomy In most organisms chromosome loss is a more frequent vent than chromosome gain Monosomy usually results in more harmful effects and is more common than trisomy however monosomy isn t seen in abortions because they take place before pregnancy is recognized Down syndrome results from three copies of chromosome 21 others are 13 and 18 Most cases of Down syndrome are caused by nondisjunction About of the trisomy 21 fetuses also undergo spontaneous abortion One reason for the nondisjunction is because chrom 21 is small and hardly undergoes crossing over preventing the formation of a chiasma which holds bivalents together Nondisjunction of chromosome 21 is more likely to occur in oogenesis than in spermatogenesis Detecting Down can be done by amniocentesis 15 16 weeks after fertilization or by chorionic villus sampling 10 11 weeks after fertilization which has a 3x risk of miscarriage Trisomic chromosomes undergo abnormal segregation In a trivalent distinct parts of one chromosome are paired with homologous parts of the others This results in one pair of gametes containing two copies and the other pair containing only one It could also form one normal bivalent and one univalent or unpaired chromosome An extra X or Y chromosome usually has a relatively mild effect This is because of the single active X principle resulting in the silencing of most x linked genes in all but 1 X chromosome in each somatic cell and the Y chromosome having few functional genes 47 XXX trisomy X female phenotypically normal mild mental disability 47 XYY double Y male tall impaired mental function 47 XXY Klinefelter male tall no normal sexual maturation sterile mild mental impairment 45 X Turner monosomy females short no sexual maturation The rate of nondisjunction can be increased by chemicals in the environment 5 3 Chromosome rearrangements can have important genetic effects A chromosome with a deletion has genes missing Among CNPs deletions account for a