What is pedigree analysis?

Introduction

Pedigree is the graphical representation of family chart which shows the inheritance of important traits of human being of two or more generations. It can be defined as a family tree or chart that is made up of symbols and lines that represents a person’s genetic family history. In a pedigree chart lines and symbols represents genetic relationship of generations related to it. The pedigree is a visual technique to document the biological relationships in families. It can determine mode of inheritance of any genetic disorder. Pedigree is analysed by genetic counsellor or medical geneticists.

In this pedigree given above, square represents male and circle represents female. The horizontal lines represent mating, that means male and female have been mating. Vertical lines moving downwards from a couple represents their children/offspring. Subsequent generations are written underneath the parental generations in given diagram. The different generations are I, II, III. The oldest individual are placed on the top and youngest on the bottom of the chart. Each generation is given roman numeral designation and individuals within the same generation are numbered from left to right.

On the basis of the result one can detect if there is any genetic abnormality in subsequent generations. The information in a pedigree, geneticist can determine the mode of inheritance of a trait. It can determine biological relationships of particular organism and ancestor. The word pedigree is derived from French word- ‘pied de grue’. It means crane’s foot.

The vertical and horizontal lines present in pedigree resembles crane’s legs with its branching toes. The pedigree can be used for different organisms like dogs, horses and humans. Its use is to find possibilities of inheriting genetic disorders. It is an ancestral line or chart that depicts lineage of an individual. A diagram showing genealogy of an individual helps to analyse inheritance of traits. It is very helpful to analyse for family diseases possibilities. It represents possibilities of acquiring phenotypes of a gene in organism and its ancestors from one generation to the next. Pedigree is mostly used for horses, dogs and humans. 

A pedigree provides us the information to determine our family information in easily readable charts. Pedigree uses standardise symbols only. If the sex of person is unidentified then diamond shape is used as symbol.

Someone with the phenotype represented by filled in symbol. Heterozygotes are represented by a shade dot inside symbol. The offspring are correlated to each other by horizontal line. The sibling is drawn in order of their birth from left to right. If offspring are twins, then they are connected with triangle. If the offspring dies because of some reason then, its symbol is crossed by a line. If offspring is stillborn or aborted, then represented by small triangle. The individuals of same generations are given Arabic numbers (1,2,3, 4,.. soon). Analysis is based on Mendelian inheritance. It enables us to find if the trait is dominant or recessive. Pedigrees are generally drawn after that family member who has any genetic disorder. And that individual is known as proband, indicated by arrow.

Pedigree in simple language is record of ancestry or purity of breed. Listing of pedigrees of horses, dogs, etc. are known as studbooks. Listing of pedigrees of cattle, swine, sheep, etc. are known as herdbooks. Such books are organised by governmental or private record associations or breed organizations in many countries. Possession of character under study is shown by blackened symbol. Absence of character under study is shown by clear symbol. 

The symbols used in human pedigree charts are

 pedigree analysis is also helpful to represent different aspects of a pedigree. First we collect phenotypic data from several generations and the pedigree chart is drawn. After careful observation we get whether the trait is dominant or recessive.

It helps the genetic counsellor to help the intended couple about the possibility of disease in the next generations.

Functions of pedigree

The major function of pedigree is to get an easy and readable chart which can detect various characteristics or disorders in an individual. It can be used for detecting basic characteristics like earlobes, chin shape, or a genetic disorder like colour-blindness, sickle cell anaemia disease. Besides its use in studying familial characteristics in humans, pedigree is extensively used in animals that are bred selectively for cross breeding. Pedigree represents ancestral characteristic in animal which makes easier to detect if a character will be shown in offspring or not. Use of symbols in pedigree chart makes easier for genetics studies.

Understanding Gene and Allele

What is gene?

It is the basic unit of inheritance. It is stably passed from one generation to another generation through gametes. It contains information for expression of a particular trait or character. The term gene is given by Johanssen. Mendel called it as factors or unit factor 

Genes are made up of DNA and it gives instructions to make proteins. Gene can be made up of 100s of bases or 1millon of bases. It varies in size. Each individual has two copies of same gene. Each copy is known as allele. 

What is allele?

Alleles are slightly modified or different form of same gene formed through mutations. Gene which codes for a pair of contrasting traits are known as alleles. They are also known as allelomorphs. The term allele is given by Batson.

Alleles are alternative form of gene. they are located in a specific position on specific chromosome. These are passes on to offspring from parents through gametes. Each parent contributes to one of the allele. 

The process of transmission of alleles from parents to offspring was discovered by Mendel and formulated in what is known as Mendel’s law of segregation. 

Alleles can be dominant or recessive.

Dominant allele 

This allele expresses in both homozygous and heterozygous condition or It expresses in the presence of its contrasting allele. It represents original type. Morgan called it wild type. Its symbol in Morgan genetics is t+.

Recessive allele

This allele expresses only in the presence of it identical allele. This allele expresses only in homozygous condition. It is also known as mutant type.

Homozygous condition 

A diploid individual having similar alleles are known as homozygous condition. For example, TT is homozygous tall. it is homozygous recessive. The term is given by Bateson.

Heterozygous condition

A diploid individual having dissimilar alleles are known as heterozygous condition. For example, Tt is heterozygous tall.

What are dominant and recessive?

Here dominant and recessive genes tell the inheritance pattern of particular traits. It tells us the pattern of passing over phenotypes from one generation to another generation that is from parent to offspring. 

Every sexually reproducing organism have two sets of each gene. The two copies, are known as alleles. These alleles are slightly different from each other. These alleles are responsible for formation of particular protein for particular allele. These protein expresses in individual. The proteins produced by each allele is different. Hence each allele expresses slightly different protein. This difference in allele causes different expression. It controls when, where, and how much protein is produced. Protein brings out the difference in traits. Different protein makes different phenotypes.

An allele has one dominant and one recessive allele. The one which expresses in that individual is dominant allele. The one which doesn’t express in individual is recessive allele. The dominant allele produces dominant phenotype in individual. This dominant allele comes from one parent or both the parents. The recessive allele produces recessive phenotype. The individual has two copies, one from each parents. An individual with one dominant and one recessive allele has dominant phenotype. As well as individual with two dominant alleles represent dominant phenotype. The one with both dominant and recessive alleles are considered as ‘carriers’ of recessive allele. Dominant and recessive are useful concept to predict the probability of an individual inheriting certain phenotypes, especially genetic disorders. There no universal mechanism by which any dominant and recessive allele act.

Dominant allele doesn’t repress recessive allele or don’t physically dominate recessive allele. If an allele is dominant or recessive depends upon the protein they code for. The same allele can be dominant or recessive allele depending on how you look at it.

For example, sickle cell allele

Sickle cell allele inheritance patterns 

Sickle cell disease is condition where it causes pain and damage to organs and muscles of the patient. In the condition the RBC which is oval/round blood cells becomes sickle-shaped cells. The sickle-shaped RBCs get trapped in capillaries and hence block the passage for blood to flow. Because of what muscles and organ cells don’t get enough blood supply and hence not enough oxygen and nutrients, which cause them to die.

The diseases cause is in recessive pattern, that means person which both the alleles of sickle cell will have the disease. Person with only one allele of sickle cell will not have the disease. Such a person is known as carrier for sickle cell.

The sickle cell allele makes the patient resistant to malaria. Malaria-resistant has dominance inheritance pattern. The person with just one allele of sickle cell will be immune to malaria.

Common Myths Explained 

The topic dominant and recessive allele are commonly overemphasized.

1.     Dominant phenotypes are always more common than recessive phenotype

  • Dominant allele + dominant allele = dominant phenotype
  • Dominant allele + recessive allele = dominant phenotype
  • Recessive allele + recessive allele = recessive phenotype

Some people might conclude that dominant allele is twice common than recessive but it is wrong. A recessive allele can be present more frequently than dominant allele 

2.     Dominant alleles are not better than recessive alleles

Inheritance of any trait has nothing to do with whether an allele benefits a person or not. For instance, a rock pocket mouse, where fur colour is controlled by a single gene. The dark fur allele is dominant and light fur allele is recessive. When mice live in dark shady place then dark fur is better so that it will not be visible to predator. But when mice live in habitat filled with light than light fur is better. It’s the environment which tells where it is dominant or recessive.

3.    A broken allele can have a dominant inheritance pattern

In many of genetic disorders occurs due to some broken allele because of which the protein to which it was coding does not work properly. In some cases, it might be possible that one of the allele is normal. In such a cases it is recessive pattern of inheritance. But not all the diseases alleles are recessive. Keratin protein is responsible for making strengthen hair, fingernails, skin, etc. there are many disorders related to keratin protein because of defect in keratin gene, and mainly they have dominance inheritance pattern. In most of the cases it is due to single gene.

FOR EXAMPLE

 

Expected pattern for various types of inheritance in pedigree

1.    Autosomal recessive inheritance

it occurs when an individual has both the copies of an altered gene, that is one copy from each parent. Person with both the copies of particular altered gene are homozygotes. Whereas in case of parent, they would have only one altered gene hence they are heterozygotes. Such an individual with only one altered gene is known as carrier. The carrier will not have disorder but their offspring can have. The alternation should be present to cause sufficient impairment in the patient. As the name suggests it occurs in autosome. That is the altered gene is present in autosome. The parents must be carriers 

For example 

In above pedigree the male is carrier but the female, he is mating with didn’t have the altered gene hence their offspring don’t acquire disorder.

Some of the features of autosomal recessive inheritance: –

  •  Male and female both have equal chance to acquire that altered gene.
  • Person is generally in one sibship in one of its generation.
  • If both parents have chance of having one or more common ancestor in common, it increases the probability that a condition presenting in child of their may be due to both parents being carrier for same recessive gene.

If both the parent are carriers, then there is 25% chance of child being unaffected. That means may be one of their child would be unaffected.  Affected parent can have only affected children that is for aa crosses with aa can have only aa (affected) offspring. Unaffected parent can also have affected children that means it both the parents are carrier hence unaffected can have affected offspring.

Example of autosomal recessive inheritance.

2.    Autosomal dominant inheritance

Autosomal dominant is one of the pattern of inheritance by an altered gene can be transferred from parent to offspring. It can pass down through many generations. It is possible that the disease is unseen yet causes disease to other generation. In such cases sometime the parent may be carrier. In case of autosomal dominant disease, the person gets affected even if he/she has one of the altered gene. Autosomal as the word suggest it is caused by only autosomal genes.

In autosomal dominant disorder if the person inherits even one altered gene that came from only one parent, it can cause disease.  In most of the cases one of the parent may also suffered from the disease that he/she passing on. 

Getting any disease inherited depends on from where or from what type of chromosome it is coming from. There are two types of set of chromosome. One is sex chromosome and other is nonsex chromosomes or autosomal chromosomes. Any genetic disorder also depends on whether the trait is dominant or recessive. Even a single alteration on each out of twenty-two chromosomes of autosome came from one of the parent or both the parent can lead to autosomal disorder. The word dominant inheritance means only one altered gene can cause disease. 

It can cause disease even if the matching gene is normal. That is if a person has AA then it is affected. If a person has Aa, then also it is affected. Here the abnormal gene is dominant. This disease can also occur even if both the parents are unaffected and don’t have abnormal gene. If a parent is suffering from an autosomal dominant disorder than there is 50% chance of having affected child. This probability is true for every pregnancy. It states that child risk of suffering from particular disease don’t depend on whether their sibling acquire that disease or not. If the child born is normal that is unaffected then he/ she cannot pass the disorder to further generation. That mean there is no carrier in this type of inheritance.  For instance, if the child has the disease then both the child and parent are diagnosed for the disease due to abnormal gene.

it is used to describe a disorder that can occur in heterozygote condition {a person with one altered and one normal gene}. In autosomal dominant one alteration is enough to cause impairment in cell functions.

3.    Sex-linked (x – linked) recessive inheritance 

X linked inheritance is the pattern which is caused due to an alteration in one of the gene of X chromosome caused impairment in cell function and can affect the males. When females have one copy of altered gene then they are carrier to disease that means they will not acquire the disease. Males have only one chromosome of X, the other sex chromosome is Y. Whereas in case of females, they have two X chromosome. As the name suggests X linked recessive condition is caused due to alteration in X chromosome. Because males have only one X chromosome therefore alteration in one X chromosome, hence develops the condition. Females having X linked recessive condition is very rare because then they have to have both X chromosomes altered. Usually other X chromosome is found to be unaltered. Therefore, in such case the disease is inactivated. The other X chromosome compensates for altered gene. The female with one altered gene on X chromosome are known as carrier for X linked recessive disorder.

It is interesting to know that males can transmit only Y chromosome to his son, therefore son is not likely to acquire disease because of father. 

For example, 

Features of X linked recessive inheritance: –

  • Males are more likely to get affected or they are affected almost exclusively.
  • The altered gene can be transmitted from carrier mother to son.
  • Affected father cannot affect son.

If the mother is carrier the percentage of daughter being carrier too is 50 %. And each son has 50% of inheriting the altered gene and being affected from the disease. 

If the father is affected from some X linked recessive disease then it son is not going to get the disease but its daughter can be carrier for the disease. 

Examples for X linked recessive condition

  • Haemophilia
  • Duchene muscular dystrophy.

When mother is carrier: –

When mother is carrier that means she has one altered gene. The altered gene when transferred to male child then he will acquire the disease. If the altered gene is transferred to female child, then she will be carrier only. She will not acquire the disease. Hence only male children will be affected, whereas female children will continue to be carrier

X linked recessive inheritance – if father is affected

In early female embryo, one of the X chromosome is inactivated that is switched off in every cell. This occurs in every cell. In such female child one of the gene is altered. That means she is carrier to X linked recessive inheritance. She can also manifest some symptoms for disease. This occurs due to less random X inactivation process, or when she doesn’t have a normal copy of gene.

4.    Sex-linked (X linked) dominant inheritance

Sex-linked dominant is the rare way of passing through the disease to children. A single altered gene on X chromosome can pass out the sex-linked dominant disease. Passing some disease from ancestors depends on type of chromosome affected. It could be autosomal or sex-linked disorder. It is also dependent on whether it is dominant or recessive. Sex-linked disease can only be transmitted through one of the sex chromosome which is either X or Y chromosome. 

Dominant inheritance can occur even when one gene is altered and other matching gene from other parent is normal. Hence here abnormal gene is dominating the other pair.

For X linked dominant disease: – if father has altered X gene then all the daughters will inherit that altered gene and ultimately to the disease. Whereas at the same time the son will be unaffected because then they will not inherit an X chromosome from their father so they will remain unaffected. That is because daughter will always inherit the X chromosome from father. If mother is carrier than 50 % of the children would be normal that is half of their children can inherit the altered gene and can have the same disease.

For example: – there is a family of four children. There were two boys and two girls in the family. Here the mother is affected {she has an altered gene which is causing disease} but father does not have the altered gene the expected probability would be: –

  • Two children {one of them be girl and one be boy} will acquire the disease.
  • Two children {one of them be girl and one be boy} will not acquire the disease.

If there are four children in that family {two boys and two girls} and the father here is affected that means he has X chromosome affected which he can pass on only to girl children. Then the expected probabilities are: – 

  • Two girls will acquire the disease.
  • Two boys will not acquire the disease.

5.    Y Linked inheritance

this type of inheritance is also known as holandric inheritance. In this type of inheritance, the altered gene is carried through Y chromosome. That clearly states that it is only present in males. The disorder would be acquired by son but not by daughters because they will not inherit Y chromosome. Here the gene involved during spermatogenesis is mapped to the Y chromosome. Generally, the male will such alteration is infertile or hypo fertile because Y chromosome is involved. This fact makes it difficult to demonstrate Y Linked inheritance. But because infertility can be treated and techniques like intracytoplasmic sperm injection (ICSI). Such techniques can treat infertility. This results in the transmission of infertility to male offspring.

Y linked inheritance is a pattern from father to all the sons. The altered phenotype matches the phenotype of the father. No female child will be affected. Y linked inheritance is rare. Because most of the Y chromosome does not cross over. 

People’s view on pedigree analysis

Twinkle Khanna’s views on pedigree analysis

The episode of a popular reality show ‘Koffee with Karan ‘caught my attention. The episode with Akshay Kumar and Twinkle Khanna was somehow related to genetics. This couple has been married since 2001. They are the parent of two children. The daughter is Nitara and the son Aarav. Akshay Kumar is a Bollywood actor and Twinkle Khanna is one of the best-selling authors. What caught my eyes was her statement where she said she got Akshay Kumar’s genome sequenced before their marriage. 

She said “kundli milane se phle, genetic chart milao “. Her statement shows that she believes that it is important to investigate medical history of our life pattern’s family members and close relatives before marrying him. As we all know people get married to have children. Which means you are introducing the genes into your family life. It is very important to know what are the diseases running in our families.

Akshay Kumar agreed to her wife’s statement. I think most of us will agree that it is more important to match genome-patris over janampatrika. Even after this episode of Koffee with Karan, google search analysis there was a massive increase in queries related to pre-marriage genetic testing from India. 

The best way for us to get understanding of this topic is to see a genetic counsellor. 

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