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 22 is a gene jungle with 545 genes 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 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

Affected individuals have DOWN SYNDROME TRISOMY 21 Affected individuals have Sparse hair 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 Robertsonian translocation 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 A new large chromosome forms from the long arms of the two different chromosomes This individual may produce unbalanced gametes

Fig. 12.17

ROBERTSONIAN TRANSLOCATION A carrier parent with 45 chromosomes one of which is the combined 14q21q, will produce 3 kinds of offspring Phenotypically and karyotypically normal Phenotypically unaffected translocation heterozygote 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 1/6000 live births Trisomy 13 Patau Syndrome 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.