Do Now: List 5 facts you know about people with Down’s Syndrome.

1) Down’s syndrome is a rare genetic disease. Fact: 1 in 691 births result in Down’s Syndrome

(6000/year) 2) Most children with Down syndrome are born

to older parents. Fact: Most children (80%) with Down Syndrome

are born to women younger than 35 years old simply because younger women have more children. However, the incidence of births of children with Down syndrome increases with the age of the women.

3) Children with Down syndrome must be placed in segregated special education programs.

Fact: Children with Down syndrome have been included in regular academic classrooms in schools across the country. The current trend in education is for full inclusion in the social and educational life of the community. Increasingly, individuals with Down Syndrome graduate from high school with regular diplomas, participate in post-secondary academic and college experiences and in some cases receive college degrees.

4) Adults with Down syndrome are unemployable.

Fact: They are being employed in small and medium-sized offices by banks, corporations, nursing homes, hotels and restaurants. They work in clerical positions, childcare, the sports field, entertainment, and the computer industry. They bring enthusiasm, reliability and dedication to their jobs.

5) Adults with Down syndrome are uable to form close interpersonal relationships:

Fact: People with Down syndrome date, socialize, and marry.

6) Down syndrome can never be cured: Fact: Researchers are making great strides in

identifying the genes on chromosome 21 that cause the phenotypic characteristics associated with the syndrome. They are optimistic that they will be able to correct or prevent these symptoms.

Nondisjunction occurs when problems with the meiotic spindle cause errors in daughter cells.◦ 1)tetrad chromosomes

do not separate properly during meiosis I.

◦ 2) sister chromatids may fail to separate during meiosis II.

Gamete + nondisjunction gamete = aneuploidy.

◦ Trisomic cells have three copies of a particular chromosome type and have 2n + 1 total chromosomes.

◦ Monosomic cells have only one copy of a particular chromosome type and have 2n - 1 chromosomes.

One aneuploid condition, Down syndrome, is due to three copies of chromosome 21.◦ It affects one in 700 children born in the United

States.

Klinefelter’s syndrome, an XXY male, occurs once in every 2000 live births.◦ These individuals have male sex organs, but are sterile.◦ There may be feminine characteristics, but their intelligence is normal.

Males with an extra Y chromosome (XYY) tend to somewhat taller than average.

Trisomy X (XXX), which occurs once in every 2000 live births, produces healthy females.

Monosomy X or Turner’s syndrome (X0), which occurs once in every 5000 births, produces phenotypic, but immature females.

Tests are also available to determine in utero if a child has a particular disorder.

One technique, amniocentesis, can be used beginning at the 14th to 16th week of pregnancy to assess the presence of a specific disease.◦ Fetal cells extracted from amniotic fluid are

cultured and karyotyped to identify some disorders.

◦ Other disorders can be identified from chemicals in the amniotic fluids.

A second technique, chorionic villus sampling (CVS) can allow faster karyotyping and can be performed as early as the eighth to tenth week of pregnancy.◦ This technique extracts a sample of fetal tissue

from the chrionic villi of the placenta.◦ This technique is not suitable for tests requiring

amniotic fluid.

Organisms with more than two complete sets of chromosomes, have undergone polypoidy.

Triploid = normal set + nondisjunction set

Polyploidy is relatively common among plants and much less common among animals.

Polyploids are more nearly normal in phenotype than aneuploids.

One extra or missing chromosome apparently upsets the genetic balance during development more than does an entire extra set of chromosomes.

Breakage of a chromosome can lead to four types of changes in chromosome structure.

A deletion occurs when a chromosome fragment lacking a centromere is lost during cell division.◦ This chromosome will be missing certain genes.

A duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid.

Deletions, even in a heterozygous state, cause severe physical and mental problems.

One syndrome, cri du chat, results from a specific deletion in chromosome 5.◦ These individuals are mentally retarded, have a

small head with unusual facial features, and a cry like the mewing of a distressed cat.

◦ This syndrome is fatal in infancy or early childhood.

An inversion occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation.

In translocation, a chromosomal fragment joins a nonhomologous chromosome.◦ Some translocations are reciprocal, others are

not.

Cystic fibrosis (strikes one of every 2,500 whites of European descent.)◦ One in 25 whites is a carrier.◦ The normal allele codes for a membrane protein that transports Cl- between cells and the environment.◦ If these channels are defective or absent, there are abnormally high extracellular levels of chloride that causes the mucus coats of certain cells to become thicker and stickier than normal.◦ This mucus build-up in the pancreas, lungs, digestive tract, and elsewhere favors bacterial infections.◦ Without treatment, affected children die before five, but with treatment can live past their late 20’s.

Chloride channeltransports salt through protein channel out of cellOsmosis: H2O follows Cl–airway

Cl–

H2O

Cl–

H2O

mucus secreting glands

bacteria & mucus build up

thickened mucus hard to secrete

normal lungs

cystic fibrosis

cells lining lungs

Cl– channel

loss of oneamino acid

delta F508

Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana)◦ strikes 1 in 3600 births

100 times greater than incidence among non-Jews

◦ non-functional enzyme fails to breakdown lipids in brain cells fats collect in cells destroying their function symptoms begin few months

after birth seizures, blindness &

degeneration of muscle & mental performance

child usually dies before 5yo

The most common inherited disease among blacks is sickle-cell disease.

◦ It affects one of 400 African Americans.

◦ It is caused by the substitution of a single amino acid in hemoglobin.

◦ When oxygen levels in the blood of an affected individual are low, sickle-cell hemoglobin crystallizes into long rods.

◦ This deforms red blood cells into a sickle shape.

PLEIOTROPHIC

pleiotrophic (single gene has many phenotypic effects) such as:

◦ 1) breakdown of red blood cells leading to anemia, fatigue, and heart failure

◦ 2) clumping and clogging of small blood vessels leading to brain damage and more frequent infections

◦ 3) accumulation of sickle cells in spleen

Substitution of one amino acid in polypeptide chain

hydrophilicamino acid

hydrophobic amino acid

2 alleles are codominant ◦ both normal & mutant hemoglobins are

synthesized in heterozygote (Aa)◦ 50% cells sickle; 50% cells normal◦ carriers usually healthy◦ sickle-cell disease

triggered under blood oxygen stress exercise

Malaria◦ single-celled eukaryote parasite spends part of

its life cycle in red blood cells In tropical Africa, where malaria is common:

◦ homozygous dominant individuals die of malaria◦ homozygous recessive individuals die of sickle

cell anemia◦ heterozygote carriers are relatively free of both

reproductive advantage High frequency of sickle

cell allele in African Americans is vestige of African roots ������

Prevalence of Malaria

Prevalence of SickleCell Anemia

A lethal dominant allele can escape elimination if it causes death at a relatively advanced age, after the individual has already passed on the lethal allele to his or her children.

One example is Huntington’s disease, a degenerative disease of the nervous system.

Dominant inheritance◦ repeated mutation on end of

chromosome 4 mutation = CAG repeats glutamine amino acid repeats in protein one of 1st genes to be identified

◦ build up of “huntingtin” protein in brain causing cell death

memory loss muscle tremors, jerky movements

“chorea” starts at age 30-50 early death

10-20 years after start

1872

Some genetic tests can be detected at birth by simple tests that are now routinely performed in hospitals.

One test can detect the presence of a recessively inherited disorder, phenyketonuria (PKU).◦ This disorder occurs in one in 10,000 to 15,000 births.◦ Individuals with this disorder accumulate the amino acid

phenylalanine and its derivative phenypyruvate in the blood to toxic levels.

◦ This leads to mental retardation.◦ If the disorder is detected, a special diet low in

phenyalalanine usually promotes normal development