ANEUPLOIDY Having too many or too few chromosomes

ANEUPLOIDY • Having too many or too few chromosomes compared to a normal genotype • Aneuploid organisms have unbalanced sets of chromosomes due to an excess or deficiency of individual chromosomes • This creates an imbalance among the genes and causes an abnormal phenotype or even death

ANEUPLOIDY • Most autosomal aneuploids are incompatible with life • Autosomal nondisjunction occurs at a reasonable high frequency in humans but the zygote does not develop • Aborts spontaneously soon after conception • Humans do not tolerate aneuploidy well, especially monosomies • Excess of chromosomes is tolerated better than a deficiency so trisomies are more viable than monosomies

TRISOMY 3 COPIES OF A SINGLE CHROMOSOME • A few types of trisomic zygotes are capable of survival • Trisomy 21 • Trisomy 18 • Trisomy 13 • Only those trisomies involving the smallest or heterochromatic chromosomes are able to survive at all

CHROMOSOME 21 • Chromosome 21 has been described as a desert harboring a million base pair stretch with only 225 genes • Chromosome 22 is a gene jungle with 545 genes

DOWN SYNDROME TRISOMY 21 • 1866, Dr. John Langdon Down noticed that about 10% of the residents at his asylum resembled each other and could be easily distinguished from the rest of his patients • Took geneticists another 90 years to determine the correct human chromosome number and it was not until 1959 that it was known that individuals with Down Syndrome have 3 copies of the smallest chromosome

DOWN SYNDROME TRISOMY 21 • Most common and best known genetic disorder • Accounts for about 10% of all mentally disabled children • Occurs in about 1/750 live births in all ethnic groups • Accounts for about 10% of all mentally disabled children • Nearly all cases occur just once within a given family • Only about 2 -5% of cases run in families

DOWN SYNDROME TRISOMY 21 • Babies with this disorder grow slowly and have poor muscle tone • Lack of muscle tone gives them a floppy appearance • Individuals are generally shorter than average • All parts of their bodies are shortened due to poor skeletal development, including the hands and fingers

DOWN SYNDROME TRISOMY 21 • Affected individuals have w Sparse hair w a protruding tongue and thick lips • Their hands have an irregular pattern of creases • Their joints are loose and they have poor reflexes • Motor development is delayed

DOWN SYNDROME TRISOMY 21 • 1/2 of the children born with Down syndrome are born with severe heart malformations • 15% of the babies die in their first year from heart abnormalities • Many others die before the age of 5 • Those who do live beyond the fifth year of life have an average life expectancy of 50 years

DOWN SYNDROME TRISOMY 21 • Leukemia is 15 -20 times more prevalent in people with Down syndrome than in the general population • Adult males have poorly developed genitals and are sterile • Adult females can have children • 1/2 of their children are born with Down syndrome

DOWN SYNDROME TRISOMY 21 • Maturation is delayed but following puberty there is a rapid onset of aging • Those over age 40 develop the black fibers of amyliod proteins in their brains • These proteins are associated with Alzheimers • The chance of a person with Trisomy 21 developing Alzheimer’s disease is 25% compared to 6% in the general population

TRISOMY 21 • Karyotyping has shown that not all of chromosome 21 has to be present in triplicate to produce Down syndrome • In a few rare individuals, the only extra chromosomal material is the distal half of the long arm of chromosome 21. • This region houses most of the genes including a gene for an enzyme involved in aging and a leukemia causing gene

ABNORMAL CHROMOSOME STRUCTURE • Structural chromosomal defects include missing, extra, or inverted genetic material within a chromosome or exchanged parts of a chromosome

TRANSLOCATION • In translocations, nonhomologous chromosomes exchange parts • 2 types w Robertsonian translocation w Reciprocal translocation

ROBERTSONIAN TRANSLOCATION Robertsonian translocation the short arms of 2 different acrocentric chromosomes break, leaving sticky ends that then cause the 2 long arms to adhere w A new large chromosome forms from the long arms of the two different chromosomes w This individual may produce unbalanced gametes

Fig. 12. 17

ROBERTSONIAN TRANSLOCATION • A carrier parent with 45 chromosomes one of which is the combined 14 q 21 q, will produce 3 kinds of offspring w Phenotypically and karyotypically normal w Phenotypically unaffected translocation heterozygote w Translocation Down syndrome individual • The risk of a carrier having a child with Down syndrome is 15% • The condition is not related to age

MATERNAL EFFECT • 1930 a maternal age effect was shown to be a factor in most cases, not the number of children in a family • Frequency of Down syndrome births increases with advancing maternal age • Women over 35 years of age produced about 25% of all the babies born with Down syndrome

FEMALE MEIOSIS • The effect may be a consequence of the long delay between prophase I and the first meiotic division in human oocytes • Human oocytes begin meiosis before the female is born • They remain in a state of suspended animation until the girl hits puberty some 10 -13 years later • Egg ovulated by a 45 year old female has been in suspended animation for 45 years • Plenty of time for something to go wrong

TRISOMY • Trisomy 18 Edward Syndrome w 1/6000 live births • Trisomy 13 Patau Syndrome w 1/12, 000 live births • Both lead to early death by 2. 5 months • Nearly all cases die during the first year of life • All suffer from profound mental retardation.