Human Genetics Biology 311 Fall 2004 Lecture 3 Chromosome Defects Reading Chap 2 pp 47 53 Outline 1 Variation in number 2 Structural abnormalities 3 Meiosis of carriers Lecture Chromosome abnormalities changes that usually visibly alter the chromosomes caused by misrepair of broken chromosomes improper recombination or improper segregation of chromosomes during mitosis or meiosis Chromosome abnormalities can affect Germ cell constitutional Somatic cell 1 Variation in chromosome number polyploidy extra sets of chromosomes 1 3 of human pregnancies very few survive to birth lethal usually caused by 2 sperm fertilizing one egg aneuploidy one extra or one missing chromosome trisomy three copies of one chromosome i e Down syndrome 47 XX 21 or 47 XY 21 have extra chromosome 21 monosomy lack of a chromosome i e Turner syndrome 45 X monosomy for the X chromosome mixoploidy different numbers of chromosomes in different cells mosaicism An individual with a somatic chromosome defect will have a chimera with different chromosome make up in different cells 1 chimera more rare Genetically different cell lineages in one individual originating from different zygotes Examples nomenclature of chromosome abnormalities Box 2 4 Numerical Abnormalities Triploidy 69 XXX 69 XXY 69 XYY all lethal Trisomy 47 XX 21 Down syndrome Monosomy 45 X Turner syndrome Mosaicism 47 XXX 46 XX Clinical consequences of numerical abnormalities Serious usually lethal Usually pleiotrophic effects Multiple abnormalities in phenotype Imbalance in levels of gene products produced Wrong number of sex chromosomes has fewer deleterious effects than wrong number of autosomes Autosomal monosomy invariably lethal in early embryo Trisomies less harmful than autosomal monosomies Trisomies 13 18 and 21 can survive until birth Trisomy 21 may survive to age 40 or longer 2 Structural chromosome abnormalities Chromosome breaks caused by Radiation damage Chemical damage Recombination Breaks usually repaired by cellular enzymes Structural abnormalities Breaks repaired incorrectly Give rise to other abnormalities when cells divide in mitosis or meiosis Balanced no net gain or loss of chromosomal material generally no effect on phenotype Unbalanced net gain or loss of chromosomal material often get effect on phenotype Examples of structural abnormalities Chromosome defect Deletion Inversion Duplication Karyotype nomenclature 46 XY del 4 p16 3 terminal deletion 46 XY inv 11 p11p15 46 XX dup 1 q22q25 insertion into Chr 2 a segment of Chr 2 2 Insertion Ring Marker extra unidentified chromosome Translocation reciprocal Translocation Robertsonian nonreciprocal 46 XX ins 2 p13q21q31 46 XYr 7 p22q36 47 XX mar 46 XX t 2 6 q35 p21 3 balanced 45 XX der 14 21 q10 q10 translocation Down syndrome Nomenclature example chromosomes 46 Sex chromosomes XY Abnormality del Chromosome affected 4 Region affected p16 3 3 Meiosis of carriers Carriers of structural abnormalities have a high risk of passing on these or other abnormalities to the gametes due to abnormal segregation of the chromosomes in meiosis or due to the nature of the products of crossing over events Example 1 Meiosis in a carrier of a balanced reciprocal translocation Fig 2 22 Zygotes produced from fertilization of the four types of gametes produced from the carrier include Normal Balanced carrier Partial trisomy and partial monosomy usually lethal Partial monosomy and partial trisomy usually lethal Thus at least half the zygotes produced would not be viable Example 2 Crossover events occurring in meiosis in heterozygotes for paracentric inversions can result in production of dicentric and acentric chromosomes which segregate in an unstable manner Example 3 Heterozygotes for pericentric inversions can have recombination events that lead to formation of duplications and deletions 3