4 3 Alterations In Chromosome Structure and Number

4. 3 Alterations In Chromosome Structure and Number Big Ideas • Errors in meiosis can lead to errors in chromosome number in gametes. Embryos that develop from these gametes will have missing or extra chromosomes • Duplication, deletion, inversion and translocation are types of damage that can occur to chromosomes during meiosis • Genetic testing can be an important part of diagnosing treating or preventing particular genetic conditions

Atypical Chromosome Numbers • In most cases, a human embryo with an atypical number of chromosomes does not survive and the mother has a miscarriage • Some embryos with atypical chromosome numbers do survive depending on which chromosomes are affected

• Trisomy: condition in which an individual has three copies of a particular chromosome • Down Syndrome (Trisomy 21): individual carries an extra copy of chromosome 21 – Characterized by mild to severe developmental delays, certain facial features, below average height

• Meiosis occurs repeatedly in a persons lifetime as the testes produce sperm or the ovaries produce eggs • Almost always the meiotic spindle distributes chromosomes to the daughter cells without error • Occasionally mistakes can occur during meiosis that alter chromosome number • Non-disjunction: occurs when homologous chromosomes do not separate during Anaphase I or Anaphase II – page 118

• This results in gametes with either missing or extra chromosomes • If an abnormal gamete produced by a nondisjunction event unites with a normal gamete in fertilization, the result is a zygote that contains an atypical number of chromosomes • Mitosis will then carry this number of chromosomes to all of the embryonic cells

Other conditions caused by non-disjunction • Trisomy 13 (Patau Syndrome): results in severe intellectual disability and physical abnormalities (heart, brain, spinal cord, eyes, muscle tone, extra digits, cleft lip); affects 1 in 16 000 births, 5 -10% live past year 1 • Trisomy 18 (Edwards Syndrome): results in severe intellectual disability and low birth weight (small cranium, heart defects); affects 1 in 5000 births, 5 -10% live past year 1 • XXY (Klinefelter Syndrome): affects male sexual development and results in testes that do not produce enough testosterone (reduces development of secondary sex characteristics); affects 1 in 500 -100 births, testosterone injections help treat this condition

Damage To Chromosome Structure • Mutation: any change to the DNA of a cell – Some mutations change only one or a few base pairs in a DNA sequence, others occur at the level of chromosomes • Large-scale mutations that damage chromosome structure can occur when something unusual happens during crossing over

• Translocation: a fragment of one chromosome attaches to a non-homologous chromosome • Ex: Translocation Down Syndrome – translocation between chromosomes 21 and 14 – inheritance of two normal copies of chromosome 14 and one that has a piece of chromosome 21 attached to it – the extra material from chromosome 21 causes Down Syndrome (like Trisomy 21)

• Sometimes translocations result in deletions • Deletion: a fragment of a chromosome is lost • Much of our DNA does not contain genes, therefore small deletions are not usually harmful • However, if the lost fragment contains one or more genes then the instructions for making certain proteins may be lost • Those proteins have specific functions in the body • Ex: Prader-Willi Syndrome – deletion of chromosome 15

• Duplication: part of a chromosome is repeated • The repeated region sometimes includes an entire gene • Interestingly, if a region is only duplicated once, the duplication may have no effect • The duplication is most likely to have an effect when duplicated multiple times • Ex: Three or more duplications on chromosome 15 results in developmental delays and seizures

• Inversion: reverses a fragment of the original chromosome • Most of the genes are still present in their normal number and some may function • However, inversions can cause problems with the synapsis of chromosomes during meiosis – Therefore someone with a chromosomal inversion may have difficulties conceiving a baby • Summary: figure 4. 39 on page 119

Genetic Testing • Modern technologies offer many ways to obtain information about the genetic makeup of an individual • Important part of diagnosing, treating or preventing illness • In addition to karyotype analysis, genetic testing can include screening for specific gene sequences

• Carrier testing: can determine if an individual carries a copy of a mutation that his or her children could inherit • A person with a family history of a genetic condition may want to undergo genetic testing to find out his or her risk of developing the condition • This type of testing is called preventative or presymptomatic testing and is usually done for disorders that appear after birth or later in a person’s life

• Diagnostic genetic testing is used to confirm a diagnosis when symptoms for a particular genetic condition are present • A human embryo becomes a fetus about seven weeks after fertilization • Prenatal testing is used to detect small-scale mutations or chromosomal alterations in a fetus – Amniocentesis: between 14 and 20 weeks of pregnancy; extraction of some amniotic fluid that surround fetus – Chorionic Villus Sampling: as early as week 8 of pregnancy; extraction of some chorionic villi from the tissue around the fetus

• Newborn screening can detect some genetic disorders at birth through simple tests • Ex: shortly after birth, newborns are screened for phenylketonuria (PKU) • PKU is an inherited disorder that results in the inability of children to break down the amino acid phenylalanine • Phenylalanine accumulation can lead to severe developmental delays – Therefore the detection of this condition can prevent retardation