Alterations in Chromosome Number or Structure

Alterations in Chromosome Number or Structure When Meiosis Goes Wrong Recall: Sources of Genetic Variation in Meiosis 1) Crossing Over: crossing over of genetic information between homologous chromosomes during prophase I 2) Random Assortment: random alignment of maternal/paternal chromosomes during metaphase I 3) Fertilization: A genetically unique egg cell is fertilized randomly by a genetically unique sperm, leading to genetic variety in the zygote What’s a Mistake in Meiosis? ● gametes with too many or too little chromosomes can lead to genetic disorders ● Chromosomes may also have structural errors (damage) that can lead to new traits being expressed ● Gametes may not survive these errors, but if they do, any resulting embryo that forms from these gametes will inherit error Atypical Chromosome Numbers ● Most embryos with abnormal chromosome numbers do not survive ○ mother may have a miscarriage ● However, some do survive… ○ e.g. Trisomy: Three copies of a chromosome ○ Down syndrome (Trisomy 21) developmental delays, distinct facial features, heart defects, impaired immune system, shorter life expectancy Non-Disjunction ● Occurs when chromosomes fail to separate properly during meiosis (anaphase I and II) ● Results in gametes with abnormal chromosome numbers ● Conditions caused by non-disjunction include: ○ Trisomy 13 (Patau syndrome) – severe disabilities, low survival rate. ○ Trisomy 18 (Edwards syndrome) – severe abnormalities, low survival rate ○ XXY (Klinefelter syndrome) – affects male development, infertility ○ Trisomy 21 (Down Syndrome) What causes non-disjunction events? ● direct correlation between a woman’s age and the likelihood of nondisjunction occurring ● Meiosis begins in the female’s ovaries before she is born but is not completed until meiosis resumes during ovulation ● Since only one egg is released each month, egg cells may remain stopped in the middle of meiosis for decades! ● Some research suggests that damage to the cell during this lag time may contribute to errors in meiosis Aneuploidy ● condition where a cell has an abnormal number of chromosomes - not a complete extra set, but one or more individual chromosomes added or missing. ● In a normal human cell: ○ ● Diploid (2n) = 46 chromosomes (23 pairs) In aneuploidy: ○ The number might be 45 or 47, depending on whether a chromosome is missing or extra ○ main cause of aneuploidy is nondisjunction ○ Some gametes get an extra chromosome (n + 1) ○ Others get one too few (n – 1) Damage to Chromosome Structure ● A mutation is any change to the DNA of a cell ● Some mutations change only one or a few base pairs in a DNA sequence ● Other mutations occur at the level of chromosomes ● Large-scale mutations that damage chromosome structure can occur when something unusual happens during crossing over 4 Main Changes to Chromosomal Structure Translocation ● occurs when a fragment of one chromosome attaches to a nonhomologous chromosome ○ e.g. Translocation Down syndrome, a condition that results when translocation occurs between chromosomes 21 and 14 ○ With translocation Down syndrome, a person inherits two normal copies of chromosome 14 and one that has a piece of chromosome 21 attached to it ○ The extra material from chromosome 21, like trisomy 21, causes Down syndrome Deletion ● occurs when a fragment of a chromosome is lost ● since much of our DNA does not contain genes, 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 Large deletions, therefore, typically have serious effects on the body ○ e.g. Prader-Willi syndrome, results from a deletion in chromosome 15 ○ Affected children have developmental delays and learning disabilities, behavioural problems, obesity, short stature, decreased muscle tone, and sex glands that produce little or no hormones Deletion Duplication ● a chromosomal change that occurs when part of a chromosome is repeated ● The repeated region sometimes includes an entire gene ● Interestingly, if a region is only repeated once, the duplication may have no effect ● If a region is repeated three or more times, as sometimes occurs on chromosome 15, the impact may include seizures and developmental delays 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 ● someone with a chromosomal inversion may have difficulties conceiving a baby Genetic Testing ● In addition to karyotype analysis, genetic testing can include screening for specific gene sequences ● Couples may wish to know their risk of passing down a condition before they have children ○ Carrier testing can determine if an individual carries a copy of a mutation that their children could inherit ● A person with a family history of a genetic condition may want to undergo genetic testing to find out their risk of developing the condition ○ called predictive or presymptomatic testing ● Diagnostic genetic testing is used to confirm a diagnosis when symptoms for a particular genetic condition are present Prenatal Testing ● 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 is a prenatal screening procedure performed between weeks 14 and 20 of pregnancy ● A physician inserts a needle into the mother’s uterus and extracts some of the amniotic fluid that surrounds the developing fetus. ● The fetal cells are then tested for genetic disorders, through a process of karyotyping or biochemical tests Prenatal Testing ● Chorionic villus sampling (CVS) is another procedure used for fetal testing ● Chorionic villi are fingerlike projections that protrude from the tissue surrounding the fetus ● A physician extracts a small sample of chorionic villi by inserting a narrow, flexible tube into the mother’s uterus ○ procedure can be conducted as early as the 8th week of pregnancy, enabling earlier detection than amniocentesis ● Unfortunately, both of these procedures pose some risk of complication and can lead to maternal bleeding, miscarriage, or premature birth ● Therefore, these procedures are usually conducted only if there is a high risk of genetic disorder Which condition is shown below? Which condition is shown below? ● Examine the karyotype on the next slide ● What type of chromosomal disorder are you looking at? (non-disjunction or chromosomal error?) ● How do you know?