L.3 Mutations & teratogens Flashcards
congenital malformations
- Disorders that are present at birth are called congenital, whether the cause is genetic, environmental, or both.
- Some congenital disorders are associated with structural defects attributable to errors in fetal development
Karyotype
- Karyotypes are usually described using a shorthand system of notations in the following order: total number of chromosomes is given first, followed by the sex chromosome complement, and finally the description of abnormalities in ascending numerical order.
- a male with trisomy 21 ⇒ 47,XY, +21
multifactorial
Polygenic traits are often affected by environmental factors
point mutation
- involves a single base pair substitution
- cause the affected codon to signify an abnormal amino acid. The inclusion of the abnormal amino acid in the sequence of the protein may or may not be of clinical significance.
- Sickle cell anemia and 1-antiprotease deiciency are examples of point mutation disorders in which a single amino acid substitution causes signiicant dysfunction.
frameshift mutation
- often changes the genetic code dramatically
- due to the addition or deletion of one or more bases, which changes the “reading frame” of the DNA sequence.
- DNA sequence is normally “read” in groups of three bases, with no spaces between codons. All of the codon triplets will be changed in the DNA downstream from a frameshift mutation, resulting in a protein with a greatly altered amino acid sequence.
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Normal male karyotype
46,XY
Female with Down’s Syndrome
47,XX,+21
Klinefelter Syndrome
- Individuals with Klinefelter syndrome usually have an extra X chromosome (an XXY genotype)
- symptoms : a lack of testosterone and include testicular atrophy and infertility, tall stature with long arms and legs, feminine hair distribution, gynecomastia (breast enlargement), high-pitched voice, and marginally impaired intelligence
- Testosterone therapy can achieve a dramatic reduction in the feminine characteristics associated with Klinefelter syndrome.
euploid
- The union of sperm and egg results in a fertilized egg (zygote) with the full complement of 46 chromosomes:
- 22 pairs of autosomes ( do not determine sex) and 2 sex chromosomes ( females get X and X from parents, males get X and Y
- 23 pairs total; 46 chromosomes = euploid
Aneuploidy
- refers to an abnormal number of chromosomes—in humans, either more or less than 46.
- Aneuploidy is most commonly caused by nondisjunction
Nondisjuction
paired homologous chromosomes fail to separate normally during either the irst or the second meiotic division
Monosomy
- When the abnormal germ cell (either has 22 or 24 chromosomes) combines with a normal germ cell containing 23 chromosomes, the resulting zygote will either be deicient by one chromosome (45) or have an extra chromosome (47).
- In anaphase lag, one chromosome lags behind and is therefore left out of the newly formed cell nucleus⇒ one daughter cell with normal number of chromosomes + one with a deiciency of one chromosome (MONOSOMY)
Polysomy
the condition of having too many chromosomes
crossing over.
- During meiosis, the homologous chromosomes normally pair up and exchange genetic alleles
- Normal crossing over involves precise gene exchange between homologues only, with no net gain or loss of DNA
long arm
(q arm)
P Arm
Short arm of a chromatid
Translocations (reciprocal or Robertsonian)

- Reciprocal translocation, no genetic material is lost and the individual may have no symptoms or disorder. However, an individual with a reciprocal translocation is at increased risk of producing abnormal gametes.
- Robertsonian translocation: The exchange of a long chromatid arm for a short one results in the formation of one very large chromosome and one very small chromosome. responsible for a rare hereditary form of Down syndrome
Isochromosomes

when the sister chromatids separate incorrectly at the centromere such that the two identical short arms remain together, as do the two long arms.
Inversion
- the removal and upside-down reinsertion of a section of chromosome
- The chromosome with an inverted section may not pair up properly, resulting in duplications or loss of genes at the time of crossing over.
- Offspring of an individual with an inversion may be affected.
deletion
- Loss of chromosomal material
- result from a break in the arm of a single chromosome, resulting in a fragment of DNA with no centromere.
- Chromosomal deletions have been associated with some forms of cancer, including retinoblastoma
- Deletions at both ends of a chromatid may cause the free ends to attach to one another, forming a ring chromosome.
- Deletions are more often “interstitial”, not “terminal” – i.e., an inner part of the chromosome is lost, rather than at the ends of the chromosomes
duplication
- extra copies of a portion of DNA.
- The consequences of duplications are generally less severe than those from loss of genetic material.
Mosaics
- Occasionally, mitotic errors in early development give rise to two or more populations of cells with different chromosomal complement, in the same individuals, a condition referred to as mosaicism
- Mosaicism affecting the sex chromosomes is relatively common. In the division of the fertilized ovum, an error may lead to one of the daughter cells receiving three sex chromosomes, whereas the other receives only one, yielding, for example, a 45,X/47, XXX mosaic. All descendent cells derived from each of these precursors have either a 47,XXX complement or a 45, X complement. Such a patient is a mosaic variant of Turner syndrome, with the extent of the phenotypic expression dependent on the number and distribution of the 45,X cells” … “Autosomal mosaicism seems to be much less common than that involving the sex chromosomes. An error in an early mitotic division affecting the autosomes usually leads to a nonviable mosaic due to the autosomal monosomy.”. One example of a viable autosomal mosaic is Down’s Syndrome Mosaics.
- (written as: 46, XY/47,XY,+21)
Phenotype
physical and biochemical attributes of an individual that are outwardly apparent.
genotype
expression of the individual’s unique genetic makeup,