Nondisjunction Mutations

Chapter 12

Nondisjunction ("not coming apart") is the failure of chromosome pairs to separate properly during cell division.• This could arise from a failure of homologous

chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis.

• The result of this error is a cell with an imbalance of chromosomes. Such a cell is said to be aneuploid.

• Loss of a single chromosome (2n-1), in which the daughter cell(s) with the defect will have one chromosome missing from one of its pairs, is referred to as a monosomy.

• Gaining a single chromosome, in which the daughter cell(s) with the defect will have one chromosome in addition to its pairs is referred to as a trisomy.

• If these gametes are fertilized, it will result in an embryo in which all the cells have an abnormal chromosome #

• Great video demo here• Narrated video here

Trisomy 21: Down syndrome

Down syndrome• The condition is characterized by a combination of major and minor

differences in structure. • Often Down syndrome is associated with some impairment of cognitive

ability and physical growth, and a particular set of facial characteristics. • Down syndrome in a fetus can be identified with amniocentesis during

pregnancy, or in a baby at birth.• Individuals with Down syndrome tend to have a lower than average

cognitive ability, often ranging from mild to moderate developmental disabilities.

• A small number have severe to profound mental disability.• The incidence of Down syndrome is estimated at 1 per 800 to 1,000

births, although it is statistically much more common with older mothers.• http://en.wikipedia.org/wiki/Down_syndrome

Trisomy 18: Edwards syndrome

Edwards syndrome• The incidence of the syndrome is estimated as one

in 3,000 live births[2]. • The incidence increases as the mother's age

increases. • The syndrome has a very low rate of survival,

resulting from heart abnormalities, kidney malformations, and other internal organ disorders.

• Only 50% of liveborn infants live to 2 months, and only 5–10% survive their first year of life.

• http://en.wikipedia.org/wiki/Edwards_syndrome

Trisomy 13: Patau syndrome

Patau syndrome• The risk of this syndrome in the offspring increases with

maternal age at pregnancy, with about 31 years being the average.[1]

• Patau syndrome affects approximately one in 10,000 live births.

• A few symptoms are:– mental & motor challenged – polydactyly (extra digits) – microcephaly low-set ears – holoprosencephaly (failure of the forebrain to divide properly). – heart and kidney defects

XXY - Klinefelter’s syndrome

Klinefelter’s syndrome

• The condition exists in roughly 1 out of every 1,000 males.• The principal effects are development of small testicles and

reduced fertility. • Some degree of language learning impairment may be

present,[7] and neuropsychological testing often reveals deficits in executive functions.[8]

• In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue).

• http://en.wikipedia.org/wiki/Klinefelter%27s_syndrome

Monosomy X: Turner’s syndrome

Turner’s syndrome• Occurring in 1 out of every 2500 girls, the syndrome manifests itself

in a number of ways. • There are characteristic physical abnormalities, such as short stature,

swelling, broad chest, low hairline, low-set ears, and webbed necks.[3] • Girls with Turner syndrome typically experience gonadal dysfunction

(non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility.

• Concurrent health concerns are also frequently present, including congenital heart disease, hypothyroidism (reduced hormone secretion by the thyroid), diabetes, vision problems, hearing concerns, and many autoimmune diseases.[4]

• Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory areas.[5]

• http://en.wikipedia.org/wiki/Turner%27s_syndrome

XYY – Jacobs syndrome

XYY• 47, XYY boys have an increased growth velocity during earliest

childhood, with an average final height approximately 7 cm above expected final height.[3]

• Severe acne was noted in a very few early case reports, but dermatologists specializing in acne now doubt the existence of a relationship with 47,XYY.[4]

• Testosterone levels (prenatally and postnatally) are normal in 47,XYY males.[5] Most 47,XYY males have normal sexual development and usually have normal fertility.

• Since XYY is not characterized by distinct physical features, the condition is usually detected only during genetic analysis for another reason.

• XYY boys have an increased risk of learning…and delayed speech and language skills.

• http://en.wikipedia.org/wiki/XYY

Prenatal detection

• Amniocentesis: a small amount of amniotic fluid, which contains fetal tissues, is extracted from the amniotic sac surrounding a developing fetus, and the fetal cells (DNA) is examined for genetic abnormalities.

• Can be performed between the 16th-20th week of pregnancy.

Prenatal detection• Chorionic Villus

Sampling (CVS): It entails getting a sample of the chorionic villus (placental tissue) and testing it. CVS usually takes place 10-12 weeks of pregnancy (earlier than amniocentesis)