Chromosomes

Cytogenetics A subdiscipline within genetics Focuses on chromosome variations Abnormal number of copies of genes or chromosomes can lead to genetic abnormalities Human genome sequence information is used to identify genes that contribute to the chromosome-related syndromes

Portrait of a Chromosome Primarily DNA and protein Described by size and shape Heterochromatin (dark) Euchromatin (light) Contains: Telomeres Origin of replication sites Centromere

Chromosomes Heterochromatin is darkly staining, contains mostly repetitive DNA Euchromatin contains more protein encoding genes Telomeres are chromosome tips composed of many repeats of TTAGGG and shorten with each cell division Centromere is the largest constriction of the chromosome and where spindle fibers attach

Centromere Position At tip  telocentric Close to end  acrocentric Displaced from center  submetacentric Long arm q Short arm p At midpoint  metacentric

Karyotype Chromosomal chart Chromosomes arranged by size and structure Arranged by largest to smallest

Visualizing Chromosomes Fetal tissue: amniocentesis chorionic villi sampling fetal cell sorting Adult tissue: blood (white blood cells) cheek swab (buccal cells) skin cells tissue biopsy

Amniocentesis Figure 13.5a

Chorionic Villi Sampling Figure 13.5b

Fetal Cell Sorting Figure 13.5c

FISHing Fluorescence in situ hybridization in situ =in tissue in vivo =in living organism in vitro =in a dish Uses a fluorescent probe to detect specific sequences of DNA

Chromosomal Abnormalities

Abnormal Chromosome # -Polyploidy An entire extra set of chromosome Example: Triploidy One egg fertilized by 2 sperm OR A diploid egg fertilized by one sperm A diploid sperm fertilizes an egg

Abnormal Chromosome # -Aneuploidy Missing a single chromosome (monosomy) OR - Having one extra chromosome (trisomy) Euploid =“good set” Aneuploid =“not good set” Caused by nondisjunction during meiosis

Nondisjunction at Meiosis I

Nondisjunction at Meiosis II

Nondisjunction at Mitosis Results in a mosaic Some cell populations are affected while others are not Severity of symptoms depends on how early in development the nondisjunction occurs.

Autosomal Aneuploids Usually lethal Those that survive often have mental retardation Most common for chromosomes 13, 18, and 21. Why?

Trisomy 21 October is Down Syndrome Awareness Month!

Table 13.6

Figure 13.7

Oogenesis Before birth After puberty (each month) Arrested in Prophase I After puberty (each month) Arrested in Metaphase II Upon fertilization

Trisomy 18 Edward syndrome Severe physical and mental disabilities Development stops at the 6 month level Oddly clenched fists Low-set ears Small mouth Unusual or absent fingerprints Liver and heart problems

Trisomy 13 Patau syndrome Fusion of the eyes or a small or absent eye Cleft lip and palate Extra fingers and toes Mental retardation

Sex Chromosome Aneuploidy

Sex Chromosome Aneuploids: Female Turner syndrome (XO) Delayed puberty 99% are not born Infertile Triplo-X (XXX) Tall stature Menstrual abnormalities All but 1 X is inactivated

Sex Chromosome Aneuploids: Male Klinefelter Syndrome (XXY) Sexually underdeveloped Small testes Sparse facial and pubic hair Long arms and legs and big feet and hands May develop breast tissue Often infertile

Sex Chromosome Aneuploids: Male XXYY Syndrome Slightly delayed childhood development Behavioral problems ADD, OCD, and learning disabilities Leg ulcers due to poor circulation Sexual development is delayed Testes do not descend Infertile Abnormal (YY) sperm AND abnormal (XX) egg

Sex Chromosome Aneuploids: Male Jacobs Syndrome (XYY) 1/1000 males has an extra Y 96% of XYY males are normal Tall height and acne Criminals with chromosomal abnormalities tend to have XYY

Abnormal Chromosome Structure Deletion =missing genetic material Can range in size (the more genes deleted, the worse the phenotype) Duplication =a region of the chromosome where genes are repeated Inversion =the DNA sequence in a region of the chromosome is inverted Translocation =a piece of the chromosome is moved to another chromosome

Translocation Nonhomologous chromosome exchange segments Two major types: Robertsonian translocation Two nonhomologous acrocentric chromosomes break at the centromere and long arms fuse. The short arms are often lost. 5% of Down syndrome results from a Robertsonian translocation between chr 21 and chr 14. Reciprocal translocation Two nonhomologous chromosomes exchange a portion of their chromosome arms.

Segregation of a Robertsonian Translocation

Reciprocal Translocation Exchange of material from one chromosome arm to another Some individuals carry a translocation but are not missing any genetic material unless a translocation breakpoint interrupts a gene

Inversions Inverted chromosomes have a region flipped in orientation 5-10% cause health problems probably due to disruption of genes at the breakpoints Inversions may impact meiotic segregation Two types of inversions occur: Paracentric inverted region does NOT include centromere Pericentric inverted region includes centromere

Segregation of a Paracentric Inversion Figure 13.21

Segregation of a Pericentric Inversion Figure 13.22

Isochromosomes Chromosomes with identical arms Form when centromeres divide along the incorrect plane during meiosis Figure 13.23

Ring Chromosomes Chromosomes shaped like a ring Occur in 1 in 25,000 conceptions May arise when telomeres are lost and sticky chromosome end fuse Radiation exposure