Chapter 6 Cytogenetics: Karyotypes and Chromosomal Aberrations

Chromosome Structure - arms P arm is the shorter (in the case of metacentric chromosome the upper) Q arm is the longer

Characteristics of Chromosome: centromere location Metacentric – centered Submetacentric – closer to one end Acrocentric – very close to end Telocentric – at the end

Chromosome Band Naming The indicated band is designated as 1q2.4 Chromosome 1 Arm q Region 2 Band 4

Karyotype Metaphase chromosomes are recorded and processed to make a karyotype Karyotypes are used to identify chromosomal abnormalities A karyotype is described by 1)the number of chromosomes 2)the sex chromosome content 3)the presence or absence of individual chromosome

Why Study Karyotypes? A karyotype provides information about the number of chromosomes, the sex of the individual, and whether there are any structural or numerical abnormalities in the chromosome set.

Karyotype A karyotype is described by 1)the number of chromosomes 2)the sex chromosome content 3)the presence or absence of individual chromosome 4)The nature & extent of any structural abnormality  t for translocation  dup for duplication  del for deletion Ex: 46,XY t(8;14)del(5p) Male w/ 46 chromosomes Translocation between chromosomes 8 & 14 Deletion of p arm of chromosome 5

Karyotype Banding There are 4 banding techniques used: G-, R-, Q-, and C-banding All except Q-banding uses a Giemsa stain G-banding is the most frequently used karyotype preparation

Cells Used for Karyotype Almost any cell that has a nucleus In adults: white blood cells (lymphocytes), skin cells (fibroblasts) Cells from biopsies and tumors Fetal cells from amniotic fluid (amniocentesis) Chorionic villis sampling removes fetal tissue from placenta by suction (can be performed earlier in pregnacy than amniocentesis)

Normal Karyotypes Normal female: 46, XXNormal male: 46, XY

Chromosomal Changes 2 Major Types of Chromosomal Changes change in chromosomal arrangement change in chromosome number

Structural Abnormalities

Change in Chromosome Number Anueploidy (individual chromosomes) & polyploidy (chromosome sets) major causes of human reproductive failure  polyploidy is rarely seen in live human births  aneuploidy is more than ten-fold higher than in other primates

Triploidy

Reasons for Polyploidy Errors in meiosis during gamete formation  homologous chromosomes fail to separate resulting in diploid gametes (2n + n = 3n triploidy) Events at fertilization  simultaneous penetration of a haploid with 2 sperm (dispermy)  75% of all cases of triploidy have 2 sets of paternal chromosomes (info gathered from analysis of spontaneous abortions) Errors in mitosis after fertilization

Aneuploidy & Nondisjunction The most common cause of aneuploidy is nondisjunction (the failure of chromosomes to separate at anaphase); more common in meiosis than in mitosis Nondisjuction during meiosis I produces all (4) abnormal gametes Nondisjuction during meiosis II produces all 2 normal gametes and 2 abnormal gametes

Nondisjunction

Autosomal Aneuploidy Autosomal monosomy is lethal Autosomal trisomy is relatively common  found in about 50% of all cases of chromosomal abnormalities in fetal death  only trisomies 8, 13, 18, & 21 result in live births  trisomy 21 is the only autosomal disorder that allows survival into adulthood

Autosomal Trisomy Causes Proposed genetic & environmental causes include: exposure to radiation genetic predisposition viral infection abnormal hormone level There is only one known risk factor - advanced maternal age

Patau Syndrome Trisomy 13 47,XX +13 or 47,XY +13

Edwards syndrome Trisomy 18 47,XX +18 or 47,XY +18

Down Syndrome Trisomy 21 47,XX +21 or 47, XY in 900 live births About 5% of cases Downs involves a Robertsonian translocation rather than a nondisjunction event

Robertsonian Translocation

Aneuploidy of Sex Chromosomes Aneuploidy of the X and Y chromosomes are more common than autosomal aneuploidy  1 in 650 for females  1 in 400 for males Monosomy for X is a viable condition Monosomy for Y is always lethal (indicates that at least one X is required for viability)

XYY Syndrome 47, XYY At one time it was thought XYY males were abnormally violent - NO STRONG EVIDENCE to support a link between XYY and violent criminal behaviors

Klinefelter Syndrome 47, XXY

Turner Syndrome 45,X