SUMAYA, JOSE ENRICO M.

BMLS II-II

PEDIGREE
Reference: pedigree chart Genealogy Glossary - About.com, a part of The New York Times Company.

A pedigree is a representation of our family tree. It shows how individuals within a family are related
to each other. We can also indicate which individuals have a particular trait or genetic condition. If we
take a pedigree, which we usually try to include at least three generations, we might be able to determine
how a particular trait is inherited. Using that information, we might be able to tell the chance that a given
individual will have the trait themselves or could pass it on to their children. There are standard ways to
draw pedigrees so that we can all look at a pedigree and understand it. We use squares to represent males
and circles to represent females. We then can number our generations with roman numerals, so the top
generation would be generation one, or Roman numeral I. Along this line, we'd indicate males and
females. We would indicate marriages between individuals with a horizontal line connecting the two
individuals. If an individual has a genetic trait, we would blacken those individuals in or shade them so
that it would be understood that they had a particular trait. We would then draw a line, a vertical line, off
the horizontal line where we would indicate any of their children that they had, and we would then
indicate if any of their children were infected. And we can do this for as many generations as we have. It's
important when we draw pedigree that we try to put in as much information as possible. So, for example,
if there have been children that died in early infancy or were stillborn, we also want to include those
individuals. And those are typically shown as very small blackened-in symbols to indicate there was a
loss of a child, either in pregnancy or early in life.
 Pedigree charts are diagrams that show the phenotypes and/or genotypes for a particular
organism and its ancestors. While commonly used in human families to track genetic diseases, they can
be used for any species and any inherited trait. Geneticists use a standardized set of symbols to represent
an individual’s sex, family relationships and phenotype. These diagrams are used to determine the mode
of inheritance of a particular disease or trait, and to predict the probability of its appearance among
offspring. Pedigree analysis is therefore an important tool in both basic research and genetic counseling.

Each pedigree chart represents all of the available information about the inheritance of a single
trait (most often a disease) within a family. The pedigree chart is therefore drawn using factual
information, but there is always some possibility of errors in this information, especially when relying on
family members’ recollections or even clinical diagnoses. In real pedigrees, further complications can
arise due to incomplete penetrance (including age of onset) and variable expressivity of disease alleles,
but for the examples presented in this book, we will presume complete accuracy of the pedigrees. A
pedigree may be drawn when trying to determine the nature of a newly discovered disease, or when an
individual with a family history of a disease wants to know the probability of passing the disease on to
their children.

The affected individual that brings the family to the attention of a geneticist is called
the proband (or propositus). If an individual is known to have symptoms of the disease (affected), the
symbol is filled in. Sometimes a half-filled in symbol is used to indicate a known carrier of a disease;
this is someone who does not have any symptoms of the disease, but who passed the disease on to
subsequent generations because they are a heterozygote. Note that when a pedigree is constructed, it is
often unknown whether a particular individual is a carrier or not, so not all carriers are always explicitly
indicated in a pedigree. For simplicity, in this chapter we will assume that the pedigrees presented are
accurate, and represent fully penetrant traits.

A pedigree results in the presentation of family information in the form of an easily readable
chart. Pedigrees use a standardized set of symbols,squares represent males and circles represent females.
Pedigree construction is a family history, and details about an earlier generation may be uncertain as
memories fade. If the sex of the person is unknown a diamond is used. Someone with the phenotype in
question is represented by a filled-in (darker) symbol. Heterozygotes, when identifiable, are indicated by
a shade dot inside a symbol or a half-filled symbol.

Relationships in a pedigree are shown as a series of lines. Parents are connected by a horizontal
line and a vertical line leads to their offspring. The offspring are connected by a horizontal sibship line
and listed in birth order from left to right. If the offspring are twins then they will be connected by a
triangle. If an offspring dies then its symbol will be crossed by a line. If the offspring is still born or
aborted it is represented by a small triangle.

Each generation is identified by a Roman numeral (I, II, III, and so on), and each individual
within the same generation is identified by an Arabic numeral (1, 2, 3, and so on). Analysis of the
pedigree using the principles of Mendelian inheritance can determine whether a trait has a dominant or
recessive pattern of inheritance. Pedigrees are often constructed after a family member afflicted with a
genetic disorder has been identified. This individual, known as the proband, is indicated on the pedigree
by an arrow.[7] These changes may occur yearly or monthly.

In a Y-linked disorder, only males can be affected. If the father is affected all sons will be affected. It
also does not skip a generation.

In mitochondrial disorders it is only passed on if the mother is affected. If the mother is affected, all
offspring will be affected. If the father is affected, he does not pass it on to his offspring.

In an Autosomal Recessive Disorder, both parents can not express the trait, however, if both are carriers,
their offspring can express the trait. Autosomal recessive disorders typically skip a generation, so
affected offspring typically have unaffected parents. With an autosomal recessive disorder, both males
and females are equally likely to be affected.

Autosomal Dominant disorders don't skip a generation, so affected offspring have affected parents. One
parent must have the disorder for its offspring to be affected. Both males and females are equally likely
to be affected, so it is an autosomal disorder.

 
 

In a X-linked Recessive Disorder, males are more likely to be affected than females. Affected sons
typically have unaffected mothers. The father also must be affected for daughter to be affected and the
mother must be affected or a carrier for the daughter to be affected. The disorder is also never passed
from father to son. Only females can be carriers for the disorders. X-linked recessive disorders also
typically skip a generation.

In a X-Linked Dominant disorder, if the father is affected all daughters will be affected and no sons will
be affected. It doesn't skip a generation and if the mother is affected she has a 50% chance of passing it
onto her offspring.

In England and Wales pedigrees are officially recorded in the College of Arms, which has records

going back to the Middle Ages, including pedigrees collected during roving inquiries by its heralds during
the sixteenth and seventeenth centuries. The purpose of these heraldic visitations was to register and
regulate the use of coats of arms. Those who claimed the right to bear arms had to provide proof either of
a grant of arms to them by the College, or of descent from an ancestor entitled to arms. It was for this
reason that pedigrees were recorded by the visitations. Pedigrees continue to be registered at the College
of Arms and kept up to date on a voluntary basis but they are not accessible to the general public without
payment of a fee.

More visible, therefore, are the pedigrees recorded in published works, such as Burke's
Peerage and Burke's Landed Gentry in the United Kingdom and, in continental Europe by the Almanach
de Gotha.

A pedigree may be used to establish the probability of a child having a particular disorder or
condition. It may be used to discover where the genes in question are located (x, y, or autosome
chromosome), and to determine whether a trait is dominant or recessive. When a pedigree shows a
condition appearing in a 50:50 ratio between men and women it is considered autosomal. When the
condition predominantly affects males in the pedigree it is considered x-linked.
Some examples of dominant traits include: male baldness, astigmatism, and dwarfism. Some examples of
recessive traits include: small eyes, little body hair, and tall stature.

Given a pedigree of an uncharacterized disease or trait, one of the first tasks is to determine which
modes of inheritance are possible and then which mode of inheritance is most likely. This information is
essential in calculating the probability that the trait will be inherited in any future offspring. We will
mostly consider five major types of inheritance: autosomal dominant (AD), autosomal recessive (AR), X-
linked dominant (XD), X-linked recessive (XR), and Y-linked (Y).

Autosomal Dominant (AD)

When a disease is caused by a dominant allele of a gene, every person with that allele will show
symptoms of the disease (assuming complete penetrance), and only one disease allele needs to be
inherited for an individual to be affected. Thus, every affected individual must have an affected parent. A
pedigree with affected individuals in every generation is typical of AD diseases. However, beware that
other modes of inheritance can also show the disease in every generation, as described below. It is also
possible for an affected individual with an AD disease to have a family without any affected children, if
the affected parent is a heterozygote. This is particularly true in small families, where the probability of
every child inheriting the normal, rather than disease allele is not extremely small. Note that AD diseases
are usually rare in populations, therefore affected individuals with AD diseases tend to be heterozygotes
(otherwise, both parents would have had to been affected with the same rare disease). Achondroplastic
dwarfism, and polydactyly are both examples of human conditions that may follow an AD mode of
inheritance.

Figure 5.3:
A pedigree consistent with AD inheritance. (Original-Deyholos-CC:AN)

X-linked dominant (XD)

In X-linked dominant inheritance, the gene responsible for the disease is located on the X-chromosome,
and the allele that causes the disease is dominant to the normal allele in females. Because females have
twice as many X-chromosomes as males, females tend to be more frequently affected than males in the
population. However, not all pedigrees provide sufficient information to distinguish XD and AD. One
definitive indication that a trait is inherited as AD, and not XD, is that an affected father passes the
disease to a son; this type of transmission is not possible with XD, since males inherit their X
chromosome from their mothers.

Figure 5.4:
Two pedigrees consistent with XD inheritance. (Original-Deyholos_CC:AN)

Figure 5.5:
Some types of rickets may follow an XD mode of inheritance.
(Wikipedia-Mrish-CC:AS)

Autosomal recessive (AR)

Diseases that are inherited in an autosomal recessive pattern require that both parents of an affected
individual carry at least one copy of the disease allele. With AR traits, many individuals in a pedigree can
be carriers, probably without knowing it. Compared to pedigrees of dominant traits, AR pedigrees tend to
show fewer affected individuals and are more likely than AD or XD to “skip a generation”. Thus, the
major feature that distinguishes AR from AD or XD is that unaffected individuals can have affected
offspring.

Figure 5.6:
A pedigree consistent with AR inheritance. (Original-Deyholos_CC:AN)

Figure 5.7:
Many inborn errors of metabolism, such as phenylketonuria (PKU) are inherited as AR. Newborns are
often tested for a few of the most common metabolic diseases.
(Wikipedia-U.S. Air Force photo/Staff Sgt. Eric T. Sheler-PD)

X-linked recessive (XR)

Because males have only one X-chromosome, any male that inherits an X-linked recessive disease allele
will be affected by it (assuming complete penetrance). Therefore, in XR modes of inheritance, males tend
to be affected more frequently than females in a population. This is in contrast to AR and AD, where both
sexes tend to be affected equally, and XD, in which females are affected more frequently. Note, however,
in the small sample sizes typical of human families, it is usually not possible to accurately determine
whether one sex is affected more frequently than others. On the other hand, one feature of a pedigree that
can be used to definitively establish that an inheritance pattern is not XR is the presence of an affected
daughter from unaffected parents; because she would have had to inherit one X-chromosome from her
father, he would also have been affected in XR.

Figure 5.8:
Some forms of colour blindness are inherited as XR-traits. Colour blindness is diagnosed using tests such
as this.
Ishihara Test. (Wikipedia-unknown-PD)

Figure 5.9:
A pedigree consistent with XR inheritance. (Original-Deyholos-CC:AN)

Y-linked and Mitochondrial Inheritance.

Two additional modes are Y-linked and Mitochondrial inheritance.

Only males are affected in human Y-linked inheritance (and other species with the X/Y sex determining
system). There is only father to son transmission. This is the easiest mode of inheritance to identify, but it
is one of the rarest because there are so few genes located on the Y-chromosome. An example of Y-linked
inheritance is the hairy-ear-rim phenotype seen in some Indian families. As expected this trait is passed
on from father to all sons and no daughters. Y-chromosome DNA polymorphisms can be used to follow
the male lineage in large families or through ancient ancestral lineages. For example, the Y-chromosome
of Mongolian ruler Genghis Khan (1162-1227 CE), and his male relatives, accounts for ~8% of the Y-
chromosome lineage of men in Asia (0.5% world wide).

Mutations in Mitochondrial DNA are inherited through the maternal line (from your mother). There are
some human diseases associated with mutations in mitochondria genes. These mutations can affect both
males and females, but males cannot pass them on as the mitochondria are inherited via the egg, not the
sperm. Mitochondrial DNA polymorphisms are also used to investigate evolutionary lineages, both
ancient and recent. Because of the relative similarity of sequence mtDNA is also used in species
identification in ecology studies.