Pedigree Introduction

Question 1

How do you represent a male or female in a pedigree? How do you represent someone without defined sex?

Answer 1

Box is male, circle is female, diamond is unspecified

Question 2

How do you represent consanguinity in a pedigree?

Answer 2

Double line (instead of single line for marriage)

Question 3

How do you represent disease/disorder in a pedigree? What about death?

Answer 3

Black filling inside the person’s circle or box. Death is marked by a diagonal line across the box.

Question 4

What is the proband and consultand in a pedigree?

Answer 4

Proband is the first person in a family to present the disease. Consultand is the person you’re doing the genetic study for

Question 5

How do you represent marriage or divorce in a pedigree?

Answer 5

Marriage is a single line. Divorce has two slashes through the single line.

Question 6

How do you represent twins in a pedigree? Monozygotic? Dizygotic?

Answer 6

Diagonal, connected lines from parents to both kids. Monozygotic will have a bar between them. Dizygotic don’t have a bar (different zygotes, born at same time)

Question 7

How do you represent a carrier, and an obligate carrier, in a pedigree?

Answer 7

Carrier has a straight line through the middle. Carriers could show symptoms later in life. Obligate carriers have a small black circle in the middle.

Question 8

How are first cousins related? Second cousins? Second cousins once removed?

Answer 8

First cousins have same grandparent. Second cousins have same greatgrandparent. Second cousins once removed have same greatgrandparent, but one of the people being compared is a generation younger than the other.

Question 9

Why does early age of cancer or heart disease indicate genetic cause?

Answer 9

Cancers and heart disease can happen “naturally” as we age. If a bunch of people in the family have cancer at 80 it might just be unlucky. If a bunch of people have cancer at 40 there’s probably something going on.

Question 10

What are the most important components of a full family history?

Answer 10

Death in family, cause, age at death
Disease status in family members
Ethinicity/race/country of origin
Full or half-siblings?
Chromosome abnormalities
Pregnancy losses
Intellectual disabilities or mental conditions

Question 11

What are some red flag conditions that encourage you to consider genetic cause in disease?

Answer 11

Breast cancer under 50
Prostate cancer under 50
Colon cancer under 45
Vision loss under 55
Hearing loss under 50
Dementia under 60
Heart disease under 45
Multiple pregnancy losses
2+ medical conditions or major birth defects

Question 12

What is a dominant trait? How is it different than a recessive trait?

Answer 12

A dominant trait only takes one gene copy to cause a difference. A recessive trait requires a change in both alleles (homozygous recessive or compound heterozygous) to cause a difference.

Question 13

What is an allele?

Answer 13

A form of a gene. A given gene could have hundreds of alleles all with small changes in function.

Question 14

What is a variant?

Answer 14

A genetic difference from the “standard” human

Question 15

Draw a punnett square where both parents are heterozygous dominant. What about when one parent is homozygous dominant and the other is heterozygous dominant? What about when one is heterozygous dominant and the other is homozygous recessive? What about when one is homozygous recessive and one is homozygous dominant?

Answer 15

A) 3/4 show dominant trait
B) 4/4 show dominant trait
C) 2/4 show dominant trait
D) 4/4 show dominant trait

Question 16

What are hallmarks of an autosomal dominant pedigree?

Answer 16

Male-to-male transfer. Vertical transfer, multiple generations are hit with disease. Males and females equally likely to be affected.

Question 17

What is neurofibrosis type 1?

Answer 17

Defined as having 2 of the following 6 conditions: 6+ cafe-au-lait spots. 2 neurofibromas. axillary or groin freckling. optic glioma. 2 or more lisch nodules. bony lesions. first degree relatives with prognosis. Autosomal dominant disease, so commonly passed down family lines.
Pleiotropic (one mutation can cause different symptoms in different people)
Age related penetrance (symptoms become more apparent with age)

Question 18

What is a de novo mutation?

Answer 18

A new mutation. Something that happened uniquely in the patient, and was not transferred genetically down by parents.

Question 19

What is incomplete penetrance?

Answer 19

Someone in the family has the disease but it’s not apparent, so it looks like it skipped a generation. This could happen with breast cancer caused by BRCA1 being passed down through a dad.

Question 20

What is mosaicism in a pedigree?

Answer 20

A mosaic individual is one who has mutations in his germ cells or in her ova, which are passed down to the child, even though the person shows no symptoms and doesn’t even have a variant in most parts of the body. Someone who is mosaic for a trait wouldn’t have any side effects themselves but it would/could show up in offspring.

Question 21

What does it look like in a punnett square when both parents are heterozygous for a recessive disease?

Answer 21

1/4 no issue
2/4 carriers
1/4 disease
siblings of affected person have 2/3 chance of being carriers
recurrence risk for siblings (recurrence is likelihood of also having disease) is 25%

Question 22

What are some characteristic traits of an autosomal recessive pedigree?

Answer 22

Horizontal transmission - you’ll see most affected individuals in a single generation. Males and females are affected equally. Founder mutations (small population base, increased chance of recessive disease showing up) and consanguinity usually do damage through recessive alleles.

Question 23

What are some examples of autosomal dominant diseases?

Answer 23

neurofibromatosis 1 and 2
Huntington’s
Hereditary breast cancer

Question 24

What are some examples of autosomal recessive diseases?

Answer 24

Sickle Cell (oxygen transport messed up), cystic fibrosis (mucus is dehydrated and gets stuck in bad areas), phenylketonuria (phenylalanine hydroxylase is defunct, tyrosine can’t be made)

Question 25

What does autosomal mean?

Answer 25

Not sex chromsomes being considered

Question 26

What is a sex-limited condition?

Answer 26

If the condition is not passed down by sex chromosome but you can’t get it unless you’re a certain sex, you have a sex-limited condition.

Question 27

What is a sex influenced condition?

Answer 27

A sex influenced condition would be something like breast cancer. Guys will inherit the gene, but it doesn’t affect them because they’ve got less breast tissue and way less glandular tissue.

Question 28

What is a sex linked condition?

Answer 28

Disorder associated with genes on either the x or y chromosome. Sex linked conditions often affect guys more than girls (only one copy of each x and y chromosome, so more recessive alleles can do well)

Question 29

What is an x linked condition?

Answer 29

A condition caused by an allele coded for on one of the sex chromosomes. A male will automatically show the x-linked condition because he only has 1 x chromosome. A woman could be a carrier for the disease without knowing it, and her male children would have a 50% chance of getting the disease. If her husband was without the condition, her female children could never get the disease but would just be carriers.

Question 30

What does hemizygous mean?

Answer 30

In males with x-linked conditions. They can’t be called homozygous because there’s only one allele copy present. So they’re hemizygous.

Question 31

What is x-inactivation?

Answer 31

In a given cell, one of the x chromsomes may not be active. This is especially important in early development. X inactivation occurs at about the 32 cell stage. You could have 16 of the cells show x1 gene and 16 show x2 gene. You could potentially though, by chance, have 21 of x1 gene and 11 of x2 gene. If you have overexpression of the recessive gene you could see partial phenotypes. Associated with fragile-x syndrome

Question 32

Why does consanguinity increase risk of genetic conditions?

Answer 32

We each carry around half a dozen or so recessive conditions, but they’re rarely expressed in our kids because our partners will have a diverse set of recessive conditions with little overlap. When you marry within your family you’re going to increase the likelihood you pass down two recessive alleles to a kid.

Question 33

What are some x-linked conditions?

Answer 33

Duchenne muscular dystrophy
hemophilia A & B
hypophosphatemic rickets
incontinentia pigmenti

Question 34

What is unique about mitochondrial inheritance?

Answer 34

The mitochondria comes just from the mom, and isn’t representative of the mom’s genome. There could be errors in just the oocyte that happens to be fertilized and that mitochondria is what’s passed down to the offspring. There’s often a mix of healthy and mutant mitochondria. Mitochondrial genetic conditions cannot be passed down through men.

Question 35

What is homoplasmy/heteroplasmy?

Answer 35

Homoplasmy means you have all the same mitochondria/cytosolic functioning within your cells. Heteroplasmy means some of the mitochondria are messed up and some are healthy. If you reach a certain threshold of messed up vs. functional you’ll have an expressed condition.

Question 36

Do all mitochondrial diseases come from mitochondrial genes?

Answer 36

no! many mitochondrial proteins are coded for in the nucleus.

Question 37

What are common pedigree hallmarks for mitochondrial genetic conditions?

Answer 37

All individuals with condition are related through the maternal line. Male’s status doesn’t seem to matter in reproductive chances of passing the disease on.

Question 38

What is codominance?

Answer 38

Both alleles are dominant and expressed together, but when paired with other alleles that were recessive they would be expressed on their own, blocking out the other phenotypes.

Question 39

What is the sum rule (in probability)?

Answer 39

When events are mutually exclusive and independent, the probability that one of two events will occur is the sum of both probabilities.

Question 40

What is the product rule (in probability?)

Answer 40

When events are mutually exclusive and independent, the probability that both events will occur is the product of the probabilities of each event.

Question 41

The risk of acquiring a duck is 15% for the population. Your patient’s father loves ducks, and has an 80% risk for acquiring a duck. If loving ducks is genetic, and autosomal dominant, what is the risk that your patient will acquire a duck?

What would be the risk if she’d been tested positive for loving ducks?

Answer 41

15% * 50% (50% chance she did not get dominant trait from dad) + 80% * 50% (50% she loves ducks) = 47.5%

If loving ducks test was positive she would have an 80% risk for acquiring a duck.

Question 42

What are rules of thumb for chasing an allele through family histories?

Answer 42

If parent has gene - each child has 50% chance of being a carrier. Each sibling has a 50% of being a carrier. If you are a carrier, there’s a 50% chance you got it from your mom, 50% chance you got it from dad.

Question 43

What is huntington’s disease?

Answer 43

A progressive, non-treatable, dominant disease that expresses later in life (after having kids). Degenerative brain disease caused by loss of cells in basal ganglia (motor control). Common early symptoms are fidgeting, twitching, facial grimaces, change in handwriting, trouble with coordination skills

Question 44

What do you need to consider when doing genetic tests on a child?

Answer 44

Will the genetic test results be of timely medical benefit to the child? If the test will reveal a condition that cannot be treated, it is only going to add stress that early in life. Wait until the child is an adult and can make their own decisions.
Always be wary of taking independence and privacy away from a child. Screening should only be done when you can make things better before symptoms would have arisen.
If child is an adolescent and doesn’t want testing, don’t do it!

Question 45

What is the difference between screening and genetic testing?

Answer 45

Screening is done before symptoms are evident. Genetic testing could be done when there are family members with disease or the person has symptoms and you want to see what it’s from.

Question 46

What are some things to consider with genetic testing?

Answer 46

Medical risks: can you do anything about it? Will it cause your insurance payments to jump up?
Reproductive risks: Could your kids get the disease?
Psychosocial risk: Will you be discriminated against? Will you be stressed for the rest of your life? Will the parent see the child differently?

Question 47

What is genetic discrimination?

Answer 47

Differential and negative treatment of someone based on a genetic condition they have.

Question 48

What is adverse selection?

Answer 48

When a patient knows more about their health than a health insurer, they can choose to purchase a plan that saves them money long term. The insurer wouldn’t know to charge more because they don’t know about the diseases. But! Is it right that an insurer could bump up costs for people at higher risk?

Question 49

What does the ADA protect?

Answer 49

The ADA (americans with disabilities act) prohibits discrimination based on genetic conditions, physical disabilities, etc. Employer must make accommodations and can only fire if the person is unable to perform essential functions of job.

Question 50

What does HIPAA protect?

Answer 50

health insurance portability and accountability act of 1996 protects people (in employer-based insurance plans) from being charged extra for genetic conditions. Genetic information includes family history, genetic tests, participation in clinical research, genetic counseling sessions.

Question 51

What does GINA cover?

Answer 51

GINA is an ammendment to HIPAA. It keeps insurance companies from changing premiums based on genetic information. Protects health insurance but does not cover life insurance or disability insurance or long-term-care insurance. So you’d want to get insurance and then get the medical tests to confirm your concern.