3. Pedigree

What is a pedigree used for in genetics?

A pedigree is a graphic illustration of members' positions within a family and their medical history.

How are generations represented in a pedigree?

Generations in a pedigree are referred to by Roman numerals.

What symbol represents women in a pedigree?

Circles represent women in a pedigree.

What symbol represents men in a pedigree?

Squares represent men in a pedigree.

How are relationships depicted in a pedigree?

Lines are used to depict relationships in a pedigree.

How are individuals numbered in a pedigree?

Persons in a pedigree are numbered left to right.

In what order are siblings listed in a pedigree?

Siblings are listed in birth order, with the oldest on the left.

What do horizontal connecting lines represent in a pedigree?

Horizontal connecting lines indicate a mating in a pedigree.

What do vertical lines represent in a pedigree?

Vertical lines are lines of descent in a pedigree.

How are children represented in a pedigree?

The symbols for all children are drawn from the same vertical line.

What does a vertical line indicate in a pedigree?

A vertical line indicates a connection between parents and offspring in a pedigree.

How is the proband indicated in a pedigree?

The proband is indicated by an arrow in a pedigree.

How is a mating represented in a pedigree?

A mating is represented by a solid horizontal relationship line in a pedigree.

What does the sibling line represent in a pedigree?

The sibling line connects siblings in a pedigree.

What symbol is used to indicate a pregnancy loss in a pedigree?

A small symbol is used to indicate pregnancy loss.

What symbol is used to represent an unknown pregnancy loss?

A diamond or a triangle is used to represent an unknown pregnancy loss.

How is the sex of a fetus or embryo shown in a pedigree if it's unknown?

The sex of the fetus or embryo is indicated using a diamond (if unknown).

What does a double line indicate in a pedigree?

A double line indicates that the partners are related biologically (by blood).

What is an example of consanguinity in a pedigree?

An example of consanguinity would be first or second cousins mating.

how many generations should be included in a pedigree

3

what is the proband indicated by

an arrow

To what type of disorders do patterns of inheritance apply?

Patterns of inheritance apply to single gene disorders.

What are multifactorial conditions?

Multifactorial conditions involve more than one gene and are influenced by diet, lifestyle, environment, and genetics.

Do patterns of inheritance apply to multifactorial conditions?

No, patterns of inheritance do not apply to multifactorial conditions.

Are multifactorial conditions often familial?

Yes, multifactorial conditions are often familial.

Can you give examples of multifactorial conditions?

Examples of multifactorial conditions include hypertension and diabetes.

What does Mendelian inheritance refer to?

Mendelian inheritance refers to the rules governing the expression of single-gene or monogenic traits.

What is a single gene trait?

A single gene trait is one whose expression is controlled by the quality of its two alleles, one on each chromosome of a pair.

What is an allele?

An allele is an alternate form of a single gene.

What is a locus?

A locus is the place on a chromosome where a gene allele resides.

What is a genotype?

A genotype is the genetic makeup of a person.

What is a phenotype?

A phenotype is what we see with our eyes, the observable traits.

What is penetrance?

Penetrance refers to how often a gene is expressed within a population when the gene is present.

What happens if a gene is present but not fully penetrant?

The gene may be fully expressed, partially expressed, or not expressed at all.

What does having a highly or fully penetrant allele mean?

It means the likelihood of gene expression is nearly 100%.

What are examples of conditions associated with high penetrance?

Examples include BRCA mutations, polydactyly, and Huntington Disease.

What is expressivity?

Expressivity refers to the variance in expression of any given single-gene trait.

Is a gene always expressed with variable expressivity?

Yes, the gene is always expressed, but the degree of expression can range from slight to excessive.

What factors can modify the degree of gene expression?

The degree of expression can be modified by other genes, interactions with internal or external substances, or the environment.

What does expressivity represent in terms of gene expression?

Expressivity represents "personal" gene expression modification.

Is the degree of expression predictable across individuals or generations?

No, the degree of expression is not predictable from one person or generation to the next.

How is a single gene trait expressed in autosomal dominant transmission?

A single gene trait is expressed whether the person is homozygous or heterozygous for the gene alleles.

What happens when a person has two dominant alleles in autosomal dominant transmission?

Both dominant alleles are expressed equally.

What occurs when a dominant allele is paired with a recessive allele?

Only the dominant allele is expressed, and the recessive allele is "silent."

In conditions transmitted in a dominant fashion, what is the usual genetic state of the disease?

The disease state is usually heterozygous, where the mutated gene is not “silenced” by the partner “normal” gene.

How is the distribution of autosomal dominant traits or conditions between males and females?

Autosomal dominant traits or conditions are about equally distributed between males and females.

Is there a carrier status for autosomal dominant conditions?

No, there is no carrier status. A heterozygous person expresses the trait or condition.

How often does an autosomal dominant trait or condition appear in generations?

Autosomal dominant traits or conditions appear in every generation, transmitted from parent to child.

What is the risk for a heterozygous individual to transmit the affected allele in autosomal dominant conditions?

The risk is 50% with each pregnancy.

Dd, dd

What is the risk for a homozygous individual to transmit the affected allele in autosomal dominant conditions?

The risk is approximately 100% with each pregnancy.

Can unaffected individuals transmit an autosomal dominant trait?

No, unaffected individuals cannot transmit the trait because they do not have it.

What terms are used to describe the outcomes of offspring in autosomal dominant conditions?

The terms "affected" and "unaffected" are used.

What are some examples of autosomal dominant (AD) traits and conditions?

Achondroplasia, blood types A and B, Huntington disease, long eyelashes, Marfan syndrome, familial adenomatous polyposis, free earlobes, hereditary breast/ovarian cancer, oval face shape, straight thumbs, tongue rolling, and widow’s peak.

What does autosomal recessive (AR) transmission mean?

AR traits have controlling gene alleles on an autosomal chromosome.

When is an autosomal recessive (AR) trait expressed?

An AR trait is expressed only when both alleles are present (person is homozygous).

• aa expresses disease

• Aa is a carrier

Can an autosomal recessive (AR) allele be present without expression in a family?

Yes, an AR allele may be present for many generations without overt expression.

How is the distribution of an autosomal recessive (AR) trait/condition observed between males and females?

The trait/condition expresses nearly equal distribution between male and female family members.

When does an autosomal recessive (AR) trait/condition often appear?

It often appears first in siblings rather than in the parents of affected children.

What is assumed and verified in autosomal recessive (AR) inheritance?

Obligate carrier status is assumed and then verified.

In an autosomal recessive (AR) inheritance, does the trait/condition appear in all generations of a family?

No, the trait/condition may not appear in all generations of any one branch of a family.

What percentage of family members typically express an autosomal recessive (AR) trait?

About 25% of the members of a family with an AR trait express it.

What does carrier status mean in autosomal recessive (AR) inheritance?

Carrier status means having one affected/mutated allele without expressing the trait.

• Aa

Can unaffected carriers of an autosomal recessive (AR) trait transmit the trait?

Yes, unaffected carriers can transmit the trait to their children.

Can two carrier parents of an autosomal recessive (AR) trait have an affected child?

Yes, two carrier parents can transmit the trait and have an affected child.

Examples of autosomal recessive traits/conditions

• attached earlobes

• cleft chin

• cystic fibrosis

• short eyelashes

• sickle cell disease/trait

• square facial shape

• “hitch-hiker” thumb shape

• phenylketonuria

• straight hairline

• tay-sachs disease

What makes X and Y chromosomes unique?

X and Y chromosomes have genes not present on other chromosomes.

How many genes does the Y chromosome have?

The Y chromosome is small with fewer than 300 total genes.

What do most Y chromosome genes code for?

Most Y chromosome genes code for male sexual development.

How are Y chromosome genes inherited?

Y chromosome genes are transmitted only from father to son.

How many X chromosomes do females and males have?

Females have two X chromosomes, and males have one X chromosome.

How many alleles do females and males have for X genes?

Females have two alleles for X genes, while males have only one allele for X genes.

Why do males have dominant expression for X-linked genes?

Males have only one allele for X genes, and these alleles have no corresponding allele on the Y chromosome, leading to dominant expression (hemizygosity).

How does the incidence of an X-linked recessive trait compare between males and females?

The incidence of the trait is much higher among males than females.

Can an X-linked recessive trait be transmitted from father to son?

No, an X-linked recessive trait cannot be transmitted from father to son.

How is an X-linked recessive trait transmitted?

It is transmitted from father to all daughters and from carrier mothers to both sons and daughters.

What is the risk for female carriers of transmitting an X-linked recessive allele?

Female carriers have a 50% risk (each pregnancy) of transmitting the allele to their offspring of either gender.

1. Males (XY) have one X and one Y chromosome. Since they only have one X chromosome, if they inherit an X-linked recessive allele (Xʳ), they will express the trait because there is no second X to mask it.

2. Females (XX) have two X chromosomes. To express an X-linked recessive trait, they must inherit two copies of the recessive allele (one from each parent). If they inherit only one copy (XʳXᵈ), they will be carriers, meaning they carry the allele but do not show the trait.

What happens if no daughters or affected sons are born to affected fathers with carrier mothers?

If no daughters or affected sons are born, the trait/condition is not transmitted further.

Examples of x-linked recessive traits/disorders

• color vision (red/green)

• classic hemophilia

• Duchenne muscular dystrophy

• male pattern baldness

Where is the gene mutation for X-linked dominant traits located?

The gene mutation is on the X chromosome of either parent.

How many copies of the X-linked dominant gene mutation are needed for the condition to manifest?

Only one copy of the X-linked dominant gene mutation is needed for the condition to be manifested.

How is X-linked dominant inheritance similar to autosomal dominant inheritance?

It is similar to autosomal dominant inheritance but is sex chromosome linked.

How does an X-linked dominant trait appear across generations?

X-linked dominant traits appear in every generation.

How do affected males with X-linked dominant traits pass the condition on?

Affected males pass the condition to all affected daughters and no affected sons.

What is the chance of a child being affected if the mother has an X-linked dominant trait?

There is a 50% chance of being affected if the mother is affected.

What are examples of X-linked dominant conditions?

Examples include polydactyly (many fingers) and polycystic renal disease (usually seen in adulthood).

How is Y-chromosome inheritance passed down?

Y-chromosome inheritance is passed directly from father to son.

How many traits have been discovered on the Y chromosome?

About 3 dozen traits have been discovered on the Y chromosome.

What are some important functions of Y-chromosome traits?

Y-chromosome traits are important for male sexual development and fertility.

How are mitochondria inherited?

All mitochondria are inherited from the mother at conception.

Why does the mother contribute all mitochondria to the offspring?

The mature ovum at fertilization is large and contains more than 100,000 mitochondria, which are inherited.

Do sperm contribute mitochondria to the zygote?

No, the sperm has no mitochondria to contribute to the zygote.

How common are mitochondrial conditions?

Mitochondrial conditions are extremely rare.

In which tissues are mitochondrial problems most frequently noted?

Mitochondrial problems are most frequently noted in the musculoskeletal, cardiovascular, and neurological systems.