Lec 54: Medical Genetics I: Introduction to Medical Genetics

Question 1

Chromosomal disorders:

Answer 1

Chromosomal disorders: Due to gain or loss of segments or entire chromosomes

Question 2

Single gene disorders:

Answer 2

Single gene disorders: Due to individual mutant genes

Question 3

Multifactorial disorders:

Answer 3

Multifactorial disorders: Due to multiple genes, often acting in concert with environmental factors

Question 4

Allele:

Answer 4

Allele: one of the different forms (variants) of a gene within a population

Question 5

Homozygote:

Answer 5

Homozygote: An individual with two identical alleles

Question 6

Heterozygote:

Answer 6

Heterozygote: An individual with two different alleles

Question 7

Hemizygote:

Answer 7

Hemizygote: An individual with only one allele, chromosome or chromosome segment, instead of the usual two

Question 8

Dominant trait (or allele):

Answer 8

Dominant trait (or allele): one that is expressed in the heterozygote

Question 9

Recessive trait (or allele):

Answer 9

Recessive trait (or allele): one that is expressed only in homozygotes or hemizygotes

Question 10

Genotype:

Answer 10

Genotype: genetic constitution; the genotypic ratio in the offspring is 1CC : 2Cc : 1cc.

Question 11

Phenotype:

Answer 11

Phenotype: observable expression of genes; if c is recessive, the phenotypic ratio in the offspring is 3 normal : 1 affected.

Question 12

Carrier:

Answer 12

Carrier: heterozygote for a mutant allele; generally used for a recessive disorder.

Question 13

Explain Mendel’s insights into the nature of inheritance and how traits are transmitted from parent to offspring.

Answer 13

Each physical trait (such as plant height and flower color in peas) is controlled by a pair of hereditary determinants (genes). For each trait, an individual inherits one gene from the father and one from the mother. Law of segregation: Each gamete (oocyte or sperm) receives only one allele of a pair, and alleles segregate equally. That is, if an individual is heterozygous (Cc), half the gametes will receive the C allele, and half will receive the c allele.

Question 14

How many stages of meiosis are there and generally happens?

Answer 14

Meiosis I: Chromosomes divide (diploid) Meisosi II: Chromatids divide (haploid)

Question 15

Relate meiosis and Mendel’s laws of segregation and independent assortment of genes:

Answer 15

Accounts for Mendel’s laws of segregation and independent assortment of genes. During meiosis, the homologs segregate away from each other. Each gamete receives only one chromosome from each homologous pair and thus only one allele of each pair. This accounts for equal segregation of alleles, and allows one to predict the types and frequencies of offspring of a particular mating. The independent assortment of genes arises from the fact that each pair of chromosomes segregates independently from the others. If two genes controlling different traits are located on different chromosomes, all combinations of alleles are possible, depending on how the chromosomes line up on the equator at metaphase in meiosis I. Thus, an individual who is heterozygous for each of two gene pairs on different chromosomes (Aa Bb) would produce four kinds of gametes: AB, Ab, aB, and ab

Question 16

Describe the basic organization of chromosomes and list the major components and their characteristics.

Answer 16

Basic organization: chromosome have a telomere with a short and long arm divide by a centromere. The structure and number of chromosomes (karyotype) is characteristic for each species. A standard description of a karyotype lists the total number of chromosomes, followed by the sex chromosome constitution and a description of any chromosomal abnormalities that may be present; 46,XY indicates a normal male karyotype.

Question 17

Describe the normal human karyotype:

Answer 17

Normal karyotype: Male46, XY Female46, XX

Question 18

Telomere:

Answer 18

Telomere: chromosome end Centromere: heterochromatin to which the spindle fibers attach during cell division Metacentric: having the centromere in the middle Submetacentric: having the centromere somewhat distant from the middle Acrocentric: having the centromere near the telomere

Question 19

Centromere

Answer 19

Centromere: heterochromatin to which the spindle fibers attach during cell division

Question 20

Metacentric

Answer 20

Metacentric: having the centromere in the middle

Question 21

Submetacentric

Answer 21

Submetacentric: having the centromere somewhat distant from the middle

Question 22

Acrocentric

Answer 22

Acrocentric: having the centromere near the telomere

Question 23

Describe chromosomal numerical abnormalities:

Answer 23

Numerical abnormalities: The terms euploid and aneuploid are frequently used to refer to numerical abnormalities.

• Euploid: describes an exact multiple of the number of chromosomes in a normal gamete
• Aneuploidy usually refers to the gain or loss of a single chromosome. Aneuploidy arises during mitosis or meiosis by a failure of chromosomes to separate normally (nondisjunction). If one set of chromatids fails to separate, one of the daughter cells will be trisomic and the other will be monosomic for that particular chromosome.
  
  • If nondisjunction occurs during embryonic development, the individual will be a mosaic of normal and abnormal cells, unless the nondisjunction occurs at the first mitotic division in which case all cells will be aneuploid.
    
    • Aneuploidy for one or more chromosomes is also a common feature of human cancers.
      
      • Cancer cells can be also polyploid, i.e., have more than two complete sets of chromosomes.

Question 24

What is a chromosomal structural abnormalities?

Answer 24

Structural abnormalities: Chromosome structural abnormalities can result in the gain or loss of portions of chromosomes, chromosome fusions, inversions of portions of chromosomes or exchange of material between chromosomes.

Question 25

What is a translocation abnormality? Describe two types:

Answer 25

Translocation: exchange of chromosome segments between non-homologous chromosomes; two main types are reciprocal translocations and Robertsonian translocations.

• Reciprocal translocations: material is simply exchanged between two chromosomes.
• Robertsonian translocation: essentially a fusion at the centromere between two acrocentric chromosomes, with the loss of the short arms and the satellites.
  
  • Common Robertsonian translocations are confined to the acrocentric chromosomes 13, 14, 15, 21 and 22, because the short arms of these chromosomes contain no essential genetic material.

Question 26

Describe the following structural abnormalities: Duplication

Answer 26

Duplication: extra copy of part of a chromosome, leading to partial trisomy

Question 27

Describe the following structural abnormalities: Inversion

Answer 27

Inversion: breakage and rejoining of a chromosome segment in reverse order, pericentric if the centromere is included, paracentric if not

Question 28

Describe the following structural abnormalities: ring chromosome

Answer 28

Ring chromosome: deletion of telomeres and fusion of the broken ends to form a ring; very unstable during mitosis and frequently lost

Question 29

Describe the following structural abnormalities: insertion

Answer 29

Insertion: segment of one chromosome inserted into a non-homologous chromosome

Question 30

Describe the following structural abnormalities: isochromosome

Answer 30

Isochromosome: chromosome having one arm duplicated and the other arm lost; arises when the centromere divides abnormally and can involve either the short (ISO p) or long (ISO q) arm

Question 31

Describe the most common chromosome aberration syndromes in humans and discuss associated risk factors:

Answer 31

Trisomy:

• Down’s syndrome: trisomy 21
  
  • risk factor (maternal age)
• Trisomy 13 (Patau syndrome): typically very short life span
• Trisomy 18 (Edwards syndrome): typically very short life span

Most common aberration syndromes are on the sex chromosome:

• Turner Syndrome: Paternal non-disjunction accounts for the majority (70-80%) of Turner syndrome cases.
• Kleinfelter:
• Triple X:
• XYY: