Pedigree assembly and analysis

Question 1

Outline what pedigree analysis is

Answer 1

• It was developed to understand the inheritance of genes from parents to offspring (as mating patterns in humans cannot be scientifically manipulated)
• Developed as a chart that can represent a family tree with family members and their genetic traits
• It is the analysis of the results of mating
• It can reveal basic modes/patterns of inheritance
• Only shows mendelian inheritance (the presence or absence of a trait within a family across generations)

Question 2

State some structural/visual features of a pedigree chart

Answer 2

• Male = square
• Female = circle
• Marriage/mating = line connecting two symbols at the centre
• Separated/divorced = two diagonal hash marks in marriage line
• Offspring = vertical line from the centre of mating line to centre of the offspring/sibling line
• Adopted = square brackets
• Deceased = single diagonal line through square or circle
• Affected person = coloured symbol
• Carrier = half coloured symbol
• Consanguineous marriage = double marriage/mating line
• Consultand = arrow pointing to symbol
• Monzygotic twins = two diagonal vertical lines connected at the top to form a triangle
• Dizygotic twins = two diagonal vertical lines with no top triangle

Question 3

Outline the autosomal recessive pedigree pattern

Answer 3

• Both sexes are affected (autosomal location)
• Unaffected parents can have affected offspring (as it is recessive)
• Carriers are unaffected by symptoms
• Condition can ‘skip generations’
• Gives rise to lateral mode of transmission
• E.g., OCA (Oculocutaneous Albinism)

Question 4

Outline the autosomal dominant pedigree pattern

Answer 4

• Vertical mode of transmission in pedigrees
• Carriers are affected by symptoms
• Often a late onset
• Both sexes affected
• e.g., Huntington’s disease

Question 5

Outline lateral transmission

Answer 5

• Transmission of a disease from one animal to another except from the parent to the offspring
• Generally this is the transmission between two animals alive at the same time and for one to be exposed to the agent from the other

Question 6

Outline vertical transmission

Answer 6

• The transmission of an illness from the parent(s) to the offspring

Question 7

Outline the sex-linked pedigree pattern: x-linked

Answer 7

• Only males affected (indicated gene is on the x chromosome)
• Female carriers
• Carriers are unaffected by symptoms
• E.g., haemophilia

Question 8

Give some examples of human traits caused by dominant inheritance:

Answer 8

• Long sightedness
• Freckles
• Widows peak
• Broad lips
• Arched feet

Question 9

Give some examples of human traits caused by recessive inheritance:

Answer 9

• Normal vision
• No freckles
• Straight hairline
• Thin lips
• Flat feet
• Cystic fibrosis

Question 10

Give some examples of human traits caused by sex-linked inheritance:

Answer 10

• X-linked: colour blindness, haemophilia
• Y-linked: holandric male infertility

Question 11

State two modes of transmission

Answer 11

• Dominance: whether the disease alleles are dominant or recessive
• Linkage: whether the disease alleles are X-linked (on the x chromosome) or autosomal (a numbered, non-sex chromosome)

Question 12

Outline autosomal chromosomes

Answer 12

• The 22 chromosome pairs other than the XX (female) or XY (male) sex chromosomes

Question 13

What does it mean to be hemizygous?

Answer 13

• It is an individual who has only one member of a chromosome pair or chromosome segment, rather than the usual two
• Hemizygosity is often used to describe X-linked genes in males who have only one X chromosome.

Question 14

How many alleles do humans have for each of their autosomal genes?

Answer 14

• Two alleles
• Females have 2 alleles of X-linked genes, males have one allele of X-linked genes and one of Y-linked genes

Question 15

Outline three general assumptions of pedigree analysis

Answer 15

• Complete penetrance = an individual in the pedigree will be affected when they carry at least one dominant allele of a dominant trait, or two recessive alleles of a recessive one
• Rare-in-population = the trait in question is rare in the general population. It is assumed that individuals who marry into the pedigree in second and third generations are not carriers (does not including founding parents)
• Not-Y-linked = the causative genes may be autosomal or X-linked, but NOT Y-linked

Question 16

Outline five key clues when looking into a pedigree analysis

Answer 16

1. An unaffected individual cannot have any alleles of a dominant trait
2. Individuals marrying into the family are assumed to have NO disease alleles
3. An unaffected individual can be a carrier of a recessive trait
4. When a trait is X-linked, a single recessive allele is sufficient for a male to be affected
5. A farther transmits his allele of X-linked genes to his daughters, but not to his sons. A mother transmits an allele of X-linked genes to both her daughters and sons.

Question 17

Outline what patterns can indicate a recessive trait

Answer 17

• It must be recessive if any affected individual has two unaffected parents
• Since it is genetic, at least one parent MUST have an allele
• Thus, it cannot be dominant

Question 18

What patterns indicate an autosomal recessive trait?

Answer 18

• If any affected founding DAUGHTER has two unaffected parents, the disease must be autosomal recessive
• An affected individual must inherit the recessive allele from both parents, so both must have an allele
• If the father had a recessive X-linked allele, he would HAVE to be affected (he only has one X-linked allele)

Question 19

What patterns indicate a recessive trait?

Answer 19

• If any affected founding SON has two unaffected parents, we cannot determine if the recessive disease is autosomal or x-linked
• If the trait is autosomal, both parents can be unaffected carriers of the disease
• If it is X-linked, the son must have inherited his allele from his mother only

Question 20

What patterns indicate a X-linked recessive trait?

Answer 20

• When any affected NON-FOUNDING SON has two unaffected parents, the disease must be X-linked recessive
• The farther (marrying in) does not have any disease alleles, so the son inherits an allele from his affected mother
• A male cannot be affected by a single autosomal recessive allele, but can be by a single X-linked recessive allele

Question 21

Outline what patterns can indicate a dominant trait

Answer 21

• The disease must be dominant if every affected child of NON-FOUNDING parents has an affected parent
• The unaffected mother, marrying in, does not carry an allele for the disease, so the child inherits it only from the affected farther

Question 22

Outline what patterns can indicate a dominant trait

Answer 22

• The disease must be dominant is every affected child of NON-FOUNDING parents has an affected parent
• The unaffected mother, marrying in, does not carry an allele for the disease, so the child inherits it only from the affected farther
• If any affected NON-FOUNDING DAUGHTER has an affected farther, we cannot determine if the dominant disease is autosomal or x-linked

Question 23

What patterns indicate an autosomal dominant trait?

Answer 23

• When an affected son of non-founding parents has an affected farther

Question 24

What patterns indicate a X-linked dominant trait?

Answer 24

• A farther does not transmit X-linked alleles to a son, so the disease CANNOT be X-linked dominant

Question 25

What is a Heterozygote carrier?

Answer 25

• Being heterozygous means someone has two different alleles
• They inherited a different version from each parent
• In a heterozygous genotype, the dominant allele overrules the recessive one
• Therefore, the dominant trait will be expressed
• The recessive trait won’t show, but you’re still a carrier.

Question 26

What advantages does a heterozygote carrier have?

Answer 26

• This is when a single copy of a disease allele doesn‘t result in a disease but instead is good for the person or organism that carries it
• An example of sickle cell trait, which protects against malaria in heterozygotes (carriers), but causes a deadly disease in homozygotes (those affected)

Question 27

What is a key example of a heterozygote carrier advantage?

Answer 27

• Cystic fibrosis is another example; carriers are healthy and are more resistant to typhoid fever than to normal people, due to having half the CFTR Cl- channels of an unaffected individual
• This leads to a greater ability to recover from diseases which result in severe, acute diarrhoea, as it limits fluid loss.

Question 28

Why is carrier frequency for CF higher in EU Caucasians?

Answer 28

• To better deal with global diseases and competing selective pressures in hot countries (leading to fluid loss)