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 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 translocationReciprocal 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.