3.4 inheritance

Question 1

what is the difference between a gamete and a typical somatic cell?

Answer 1

GAMETES:

• haploid
• contain only 1 allele of the gene
• 2 alleles of each gene separate into different haploid nuclei during meiosis

Question 2

what are the different types of zygosity?

Answer 2

• gametes are haploid, meaning they only possess 1 allele for each gene
• when male and female gametes fuse during fertilisation, the resulting zygote will contain 2 alleles for each gene
• exception: males have only 1 allele for each gene located on a sex chromosome, as these chromosomes aren’t paired (XY)

DIFFERENT TYPES OF ZYGOSITY: [combination of alleles]

1. homozygous: if maternal and paternal alleles are same, offspring is said to be homozygous for that gene
2. heterozygous: if maternal and paternal alleles are different, offspring is said to be heterozygous for that gene
3. hemizygous: males only have 1 allele for each gene located on a sex chromosome and are said to be hemizygous for that gene

Question 3

what is the difference between genotype and phenotype?

Answer 3

GENOTYPE:

• gene composition (i.e. allele combination) for a specific trait
• genotype of a particular gene will typically be either homozygous or heterozygous

PHENOTYPE:

• observable characteristics of a specific trait (i.e. physical expression)
• determined by both genotype and environmental influences

Question 4

what is complete dominance for genes?

Answer 4

• most traits follow classical dominant / recessive pattern of inheritance, whereby 1 allele is expressed over the other
• dominant allele masks recessive allele when in a heterozygous state
• homozygous dominant and heterozygous forms will be phenotypically indistinguishable
• recessive allele will only be expressed in phenotype when in homozygous state
• when representing alleles, convention is to capitalise dominant allele and use lower case letter for recessive allele

Question 5

what is co-dominance for genes?

Answer 5

• occurs when pairs of alleles are both expressed equally in the phenotype of a heterozygous individual
• heterozygotes therefore have altered phenotype as the alleles are having a joint effect
• when representing alleles, convention is to use superscripts for different co-dominant alleles (recessive still lower case)

Question 6

outline the inheritance of abo blood groups

Answer 6

• human red blood cells can be categorised into different blood groups based on structure of a surface glycoprotein (antigen)
• abo blood groups are controlled by a single gene with multiple alleles (A, B, O)
• A, B, O alleles all produce a basic antigen on the surface of red blood cells
• A and B alleles are co-dominant and each modify the structure of the antigen to produce different variants
• O allele is recessive and does not modify basic antigenic structure
• when representing blood group alleles, letter I is used to represent different antigenic forms (isoantigens)
• A allele = IA ; B allele = IB ; O allele = i (recessive)
• as humans produce antibodies against foreign antigens, blood transfusions are not compatible between certain blood groups
• AB blood groups can receive blood from any other type (as they already possess both antigenic variants on their cells)
• A blood groups cannot receive B blood or AB blood (as the isoantigen produced by the B allele is foreign)
• B blood groups cannot receive A blood or AB blood (as the isoantigen produced by the A allele is foreign)
• O blood groups can only receive transfusions from other O blood donor (both antigenic variants are foreign)

Question 7

what is the consequence of an incompatible blood transfusion?

Answer 7

• surface antigens (on rbc) + opposing antibodies (in blood plasma) –> agglutination (clumping) –> haemolysis (lysis / rupturing of rbc)

Question 8

what are genetic diseases and what are the different types of genetic diseases?

Answer 8

• caused when mutations to a gene (or genes) abrogate normal cellular function, leading to development of a disease phenotype
• genetic diseases can be caused by recessive, dominant or co-dominant alleles

AUTOSOMAL RECESSIVE GENETIC DISEASE

• will only occur if both alleles are faulty
• Heterozygous individuals will possess 1 copy of faulty allele but not develop disease symptoms (they are carriers)
• example of autosomal recessive genetic disease is cystic fibrosis

AUTOSOMAL DOMINANT GENETIC DISEASE

• requires 1 copy of a faulty allele to cause the disorder
• homozygous dominant and heterozygous individuals will both develop full range of disease symptoms
• example of autosomal dominant genetic disease is huntington’s disease

CAUSED BY CO-DOMINANT ALLELES

• only require 1 copy of faulty allele to occur
• heterozygous individuals will have milder symptoms due to moderating influence of a normal allele
• example of a genetic disease that displays co-dominance is sickle cell anaemia

Question 9

how is cystic fibrosis inherited?

Answer 9

• autosomal RECESSIVE disorder caused by mutation to CFTR gene on chromosome 7
• individuals with cystic fibrosis produce mucus which is unusually thick and sticky
• mucus clogs airways and secretory ducts of digestive system, leading to respiratory failure and pancreatic cysts
• heterozygous carriers who possess 1 normal allele will not develop disease symptoms

Question 10

how is huntington’s disease inherited?

Answer 10

• autosomal DOMINANT disorder caused by a mutation to the huntingtin (HTT) gene on chromosome 4
• causes death in brain cells
• HTT gene possesses a repeating trinucleotide sequence (CAG) that is usually present in low amounts (10 – 25 repeats)
• more than 28 CAG repeats is unstable and causes sequence to amplify (produce even more repeats)
• when the number of repeats exceeds ~40, huntingtin protein will misfold and cause neurodegeneration
• usually occurs in late adulthood and so symptoms usually develop noticeably in a person’s middle age (~40 years)
• symptoms of huntington’s disease include uncontrollable, spasmodic movements (chorea) and dementia

Question 11

why are genetic diseases rare?

Answer 11

• any allele that adversely affects survival and hence capacity to reproduce is unlikely to be passed on to offspring
• recessive conditions tend to be more common, as faulty allele can be present in carriers without causing disease
• dominant conditions may often have a late onset, as this does not prevent reproduction and transfer of faulty allele

Question 12

what is sex-linkage?

Answer 12

• when a gene controlling a characteristic is located on a sex chromosome (X or Y)
• Y chromosome much shorter than X chromosome and contains only a few genes (50 million bp; 78 genes)
• X chromosome is longer and contains many genes not present on Y chromosomes (153 million bp ; ~ 2,000 genes)
• sex-linked conditions are usually X-linked - as very few genes exist on shorter Y chromosome

Question 13

how do sex-linked inheritance patterns work?

Answer 13

• sex-linked inheritance patterns differ from autosomal patterns due to fact that chromosomes aren’t paired in males (XY)
• leads to expression of sex-linked traits being predominantly associated with a particularly gender
• human females have 2 X chromosomes (and therefore 2 alleles): can be either homozygous or heterozygous
• hence X-linked dominant traits more common in females (as either allele may be dominant and cause disease)
• human males have only 1 X chromosome (and therefore only 1 allele) and are hemizygous for X-linked traits
• X-linked recessive traits are more common in males, as condition cannot be masked by a second allele

following trends always hold true for X-linked conditions:

• only females can be carriers (a heterozygote for a recessive disease condition), males cannot be heterozygous carriers
• males will always inherit X-linked trait from their mother (inherit a Y chromosome from their father)
• females cannot inherit an X-linked recessive condition from an unaffected father (must receive his dominant allele)
• when assigning alleles for a sex-linked trait, the convention is to write the allele as a superscript to the sex chromosome (X)

Question 14

explain red-green colour blindness as a sex-linked genetic disease

Answer 14

• X-linked RECESSIVE condition found on non-homologous region on X chromosome
• far more common in males than in females (males cannot mask the trait as a carrier)
• XA = unaffected (normal vision) ; Xa = affected (colour blindness)
• genetic disorder whereby individual fails to discriminate between red and green hues
• condition caused by mutation to red (OPN1LW) or green (OPN1MW) retinal photoreceptors, which are located on X chromosome
• red-green colour blindness can be diagnosed using ishihara colour test
• X^N : normal X, X^C: colourblind X, Y: y
• OPN1MW (green) and OPN1LW (red) alleles responsible for producing photoreceptive pigments in cone cells of eyes is found in locus Xq28 –> non-homologous region

Question 15

explain haemophilia as a sex-linked genetic disease

Answer 15

• X-linked RECESSIVE condition
• far more common in males than in females (males cannot mask the trait as a carrier)
• XH = unaffected (normal blood clotting) ; Xh = affected (haemophilia)
• genetic disorder where body’s ability to control blood clotting (and hence stop bleeding) is impaired
• formation of a blood clot is controlled by a cascade of coagulation factors whose genes are located on the X chromosome
• when 1 of these factors becomes defective, fibrin formation is prevented - meaning bleeding continues for a long time
• different forms of haemophilia can occur, based on which specific coagulation factor is mutated (e.g. haemophilia A = factor VIII)

Question 16

what are the different ways mutation can be caused?

Answer 16

• gene mutation is a change to the base sequence of a gene that can affect the structure and function of the protein it encodes
• can be spontaneous (caused by copying errors during dna replication) or induced by exposure to external elements

INDUCED
examples of factors which can induce mutations include:
- radiation – e.g. UV radiation from the sun, gamma radiation from radioisotopes, X-rays from medical equipment
- chemical – e.g. reactive oxygen species (found in pollutants), alkylating agents (found in cigarettes)
- biological agents – e.g. bacteria (such as helicobacter pylori), viruses (such as human papilloma virus)

• agents which increase rate of genetic mutations are called mutagens, and can lead to the formation of genetic diseases
• mutagens which lead to the formation of cancer are more specifically referred to as carcinogens

Question 17

what are the consequences of radiation as seen after nuclear bombing of hiroshima and accident at chernobyl?

Answer 17

• nuclear bombing of hiroshima and accident at chernobyl are 2 examples of a catastrophic release of radioactive material
• nuclear bombing of Hiroshima (and Nagasaki) occurred in August 1945, during final stages of World War II
• chernobyl accident occurred in April 1986, when an explosion at the reactor core caused release of radioactive material
• of the 2 incidents, more people died from nuclear bombing, but meltdown released far more radiation (~400×)
• chernobyl meltdown involved far more fissionable material and produced different isotopes with much longer half-lives
• hiroshima nuclear bomb was detonated above ground and radiation was dispersed, resulting in less irradiation of the soil

long-term consequences of radiation exposure following these disasters include:

• increased incidence in cancer development (with a strong correlation between dose of radiation and frequency of cancer)
• reduced T cell counts and altered immune functions, leading to higher rates of infection
• wide variety of organ-specific health effects (e.g. liver cirrhosis, cataract induction, etc.)

some of consequences of radiation exposure are specific to the incident due to the types and amounts of radiation released

• thyroid disease was a common consequence of the chernobyl accident due to the release of radioactive iodine
• no significant increase in birth defects following the Hiroshima bombing, but an estimated 250% increase in congenital abnormalities following chernobyl meltdown
• hiroshima is still habitable and well populated, but certain regions of chernobyl remain unsafe for human habitation
• anecdotal evidence to suggest that radiation levels around chernobyl have caused variation to local flora and fauna
• presence of residual radiation in environment can become concentrated in organisms via bioaccumulation

Question 18

how is phenotype determined?

Answer 18

• observable characteristics or traits of organism
• predominantly determined by organism’s genotype (allele combination) for each particular feature
• however environmental factors may also influence the expression of characteristics
• hydrangeas change colour depending on the pH of the soil (acidic soil = blue flower ; alkaline soil = pink flower)
• human skin colour is determined by the expression of melanin pigment, but levels can change depending on sun exposure

Question 19

how did mendel discover the principles of inheritance?

Answer 19

Austrian monk who developed the principles of inheritance by performing experiments on pea plants

First, he crossed different varieties of purebred pea plants, then collected and grew the seeds to determine their characteristics
Next, he crossed the offspring with each other (self-fertilization) and grew their seeds to similarly determine their characteristics
These crosses were performed many times to establish reliable data trends (over 5,000 crosses were performed)

As a result of these experiments, Mendel discovered the following things:

When he crossed two different purebred varieties together the results were not a blend – only one feature would be expressed
E.g. When purebred tall and short pea plants were crossed, all offspring developed into tall growing plants
When Mendel self-fertilised the offspring, the resulting progeny expressed the two different traits in a ratio of ~ 3:1
E.g. When the tall growing progeny were crossed, tall and short pea plants were produced in a ratio of ~ 3:1

From these findings, Mendel drew the following conclusions:

Organisms have discrete factors that determine its features (these ‘factors’ are now recognised as genes)
Furthermore, organisms possess two versions of each factor (these ‘versions’ are now recognised as alleles)
Each gamete contains only one version of each factor (sex cells are now recognised to be haploid)
Parents contribute equally to the inheritance of offspring as a result of the fusion between randomly selected egg and sperm
For each factor, one version is dominant over another and will be completely expressed if present

While there are caveats to Mendel’s conclusions, certain rules can be established:

Law of Segregation: When gametes form, alleles are separated so that each gamete carries only one allele for each gene
Law of Independent Assortment: The segregation of alleles for one gene occurs independently to that of any other gene*
Principle of Dominance: Recessive alleles will be masked by dominant alleles†

• The law of independent assortment does not hold true for genes located on the same chromosome (i.e. linked genes)
  † Not all genes show a complete dominance hierarchy – some genes show co-dominance or incomplete dominance