Chromosomal abnormalities Numerical Numerical structural structural

Abnormalities in chromosome number may orignate during meiosis and mitosis Abnormalities in chromosome number may orignate during meiosis and mitosis

etiology In meiosis two members of homologous chromosome separate during first meiotic divisionso that each daughter cell receives one member of each pair. Sometimes seperation does not occur and both members of a pair move into one cell. In meiosis two members of homologous chromosome separate during first meiotic divisionso that each daughter cell receives one member of each pair. Sometimes seperation does not occur and both members of a pair move into one cell.

Meiotic nondisjunction causes the gain or loss of single chromosomes

Non dysjunction occurs during mitosis. Such conditions produce mosaicism with some chromosome having normal number while some abnormal number. Non dysjunction occurs during mitosis. Such conditions produce mosaicism with some chromosome having normal number while some abnormal number.

Chromosome Abnormalities 1. Changes in chromosome number –Increases in entire chromosome sets (polyploidy) –Reductions or increase in ONE chromosome (aneuploidy) Aneuploidy OR presence of extra chromosome or an absence of one a. Trisomy – “three bodies” – having one extra chromosome b. Monosomy – missing a single chromosome

Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings. Fig Variations in number of complete chromosome sets

Aneuploidy: Monosomy vs. Trisomy Monosomy: results from fertilzation between one normal gamete & one gamete that is missing a chromosome. Monosomy: results from fertilzation between one normal gamete & one gamete that is missing a chromosome. In Humans: Autsosomal Monosomy extremely serious! Embryo usually ceases development very early. (considered lethal) In Humans: Autsosomal Monosomy extremely serious! Embryo usually ceases development very early. (considered lethal)

Trisomy: results from fertilization between one normal gamete & one gamete that contains an extra chromosome. Trisomy: results from fertilization between one normal gamete & one gamete that contains an extra chromosome. In Humans: Autosomal Trisomy usually results in spontaneous abortion. In Humans: Autosomal Trisomy usually results in spontaneous abortion. The only autosomal trisomies seen in live births are trisomy 13, 18 and 21. The only autosomal trisomies seen in live births are trisomy 13, 18 and 21. Trisomosy 21 (Down Syndrome) is the only autosomal trisomy that allows survival until adult hood. Trisomosy 21 (Down Syndrome) is the only autosomal trisomy that allows survival until adult hood

Down Syndrome: Trisomy 21 Distinctive physical appearance: Distinctive physical appearance: wide skull, flat in back. wide skull, flat in back. Skin fold in corner of eye, tongue furrowed & protruding, Skin fold in corner of eye, tongue furrowed & protruding, abnormalities in finger and palm prints, abnormalities in finger and palm prints, Development: Mental retardation (but large variations in mental ability), slow growth, developmental delays Development: Mental retardation (but large variations in mental ability), slow growth, developmental delays

Karyotype of a Down Syndrome Female

Slide 17 Down Syndrome: Manifestations

Prognosis: today many Down syndrome children reach adulthood. However, not many survive past 50. Prognosis: today many Down syndrome children reach adulthood. However, not many survive past 50.

Edwards Syndrome: Trisomy 18 Infant with Edwards Syndrome

Trisomy-13 (Patau syndrome) occurs in 2/10 4 live births, and most die within the first 3 months. Characteristics include i. Cleft lip and palate. ii. Small eyes. iii. Polydactyly (extra fingers and toes). iv. Mental and developmental retardation. v. Cardiac and other abnormalities

Aneuploidy Aneuploidy results from variations in the number of individual chromosomes (not sets), Aneuploidy results from variations in the number of individual chromosomes (not sets),

Sex Chromosome Aneuploidy Sex Chromosome Aneuploidy is more common than Autosome Aneuploidy! Sex Chromosome Aneuploidy is more common than Autosome Aneuploidy! In order to survive and develop embryo needs at least one X chromosome. In order to survive and develop embryo needs at least one X chromosome. In healthy females, one X chromosome will be inactivated in each somatic cell. The inactivated X chromosome is referred to as a “Barr body”. In healthy females, one X chromosome will be inactivated in each somatic cell. The inactivated X chromosome is referred to as a “Barr body”.

Female Abnormalities Turner Syndrome – only one X chromosome (XO); Turner Syndrome – only one X chromosome (XO); short, webbed necks, small jaws; lack prominent female sex characteristics; do not ovulate short, webbed necks, small jaws; lack prominent female sex characteristics; do not ovulate

Turner Syndrome Female (45 total chromosomes, 1 sex chromosome (X)) Female (45 total chromosomes, 1 sex chromosome (X)) Only monosomy that is Not lethal Only monosomy that is Not lethal Abnormalities: don’t develop normal at time of puberty, underdeveloped breasts, rudimentary ovaries Abnormalities: don’t develop normal at time of puberty, underdeveloped breasts, rudimentary ovaries Infertile: do Not ovulate or menstruate Infertile: do Not ovulate or menstruate Treatment: Hormone supplements can help these women lead normal lives Treatment: Hormone supplements can help these women lead normal lives

Male Abnormalities Klinefelter syndrome – males w/ one or more extra X chromosomes – high pitched voices, breast enlargement, sterile, testes & prostate are small; treat w extra testosterone Klinefelter syndrome – males w/ one or more extra X chromosomes – high pitched voices, breast enlargement, sterile, testes & prostate are small; treat w extra testosterone XYY syndrome – super-males; tall, seem normal; can live normal lives XYY syndrome – super-males; tall, seem normal; can live normal lives

Klinefelter Syndrome Male,( 47 total chromosomes, 3 sex chromosomes XXY) Male,( 47 total chromosomes, 3 sex chromosomes XXY) May have some learning difficulties but usually not mentally retarded May have some learning difficulties but usually not mentally retarded Affected male may not develop normally at puberty Affected male may not develop normally at puberty In severe cases: rudimentary testes & prostate gland, sparse facial and pubic hair, long arms and legs, breast development may occur In severe cases: rudimentary testes & prostate gland, sparse facial and pubic hair, long arms and legs, breast development may occur Infertility Infertility (in mild cases man may not discover disorder until he experiences infertility) (in mild cases man may not discover disorder until he experiences infertility)

Changes in chromosome structure  Translocation/Chromosomal Breaks  Deletions  Fragile sites

Chromosomal Breaks Chromosome Breaks Spontaneous breaks due to errors in DNA replication & errors in crossing-over Spontaneous breaks due to errors in DNA replication & errors in crossing-over Environmental factors: UV light, Radiation, Viruses, Chemicals Environmental factors: UV light, Radiation, Viruses, Chemicals Cri du Chat: Caused by partial deletion of Chromosome 5 Cri du Chat: Caused by partial deletion of Chromosome 5 Infant’s cry sound like a cat. Speech problems after infancy.  abnormal glottis & larynx Infant’s cry sound like a cat. Speech problems after infancy.  abnormal glottis & larynx Normal, Cri du Chat, Cat

Translocations Sometimes chromosome break and piece of one chromosome attatch to another Sometimes chromosome break and piece of one chromosome attatch to anotherBalanced Breakage and reunion occurs between chromosomesbut no genetic material is lost and individuals are normal.

unbalanced Part of one chromosome is lost and individuals are abnormal.e.g in Down syndrome an extra copy of chromosome 21

Deletion 1.In a deletion, part of a chromosome is missing.

Duplication 1. Duplications result from doubling of chromosomal segments, and occur in a range of sizes and locations.

Inversion results when a chromosome segment excises looses original orientation.

Fragile Sites Fragile X Syndrome: Makes a very thin physical region of the chromosome. Fragile X Syndrome: Makes a very thin physical region of the chromosome. Results in range of mental retardation and behavioral problems Results in range of mental retardation and behavioral problems Occurs in both sexes; Occurs in both sexes;

Why Is Non-disjunction Usually Maternal? 1. Older Mother has greater chance of non- disjunction...if woman is 40 at time of conception, approx. 40 years to complete prophase I 2. Perhaps uterus of older mother less sensitive to abmormal fetus. So older mother’s less likely to spontaneously abort abnormal fetus. 3. Or perhaps a combination of these factors….