Clinical Genetics Keya Lahiri, Mamta N Muranjan
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Clinical Genetics: Basic Principles1

Austrian Monk Gregor Mendel laid the foundation of the science of genetics in the later half of the nineteenth century. In 1865, he discovered genes and how they are inherited. As an acknowledgement of his contribution in genetics, the term Mendelian is applied to different patterns of inheritance, shown by single gene characteristics and to disorders found to be the result of defects in a single gene.
A Danish botanist termed these hereditary factors as genes. Plants with two identical genes are referred to as homozygous, whereas those hybrid plants with each gene for different characteristics would be referred to as heterozygous. The genes responsible for these characteristics are referred to as alleles.
Mendel's laws which form the cornerstone of the science of genetics, were derived from his experiments with garden peas. The three laws he derived from the results of his experiments may be stated as follows:
  1. Unit inheritance: It states that when two homozygotes with different alleles are crossed, all the offsprings in the first generation are identical and heterozygous. Thus, characteristics can be seen in later generations.
  2. Segregation: This states that each individual possesses two genes for a particular characteristic, however, only one of them can be seen transmitted at any one time. Very rarely, two allelic genes may fail to separate because of chromosome non-disjunction at the first meiotic division.
  3. Independent assortment: In reality, this is not always true as genes close together on the same chromosome tend to be inherited, i.e. they are linked.
Hereditary conditions can be classified as single gene, chromosomal, multi-factorial and acquired somatic genetic disease.
Single gene disease: There are about 8500 single gene disorders published by American physician, Victor McKusick by 1998 which are classified by their mode of inheritance (i.e., autosomal dominant, autosomal recessive, or X-linked).
Chromosomal abnormalities: These are seen in 5 in 1000 live births (0.6%). Newer banding techniques help in the identification of chromosomal abnormality. It was realized that loss or gain of even a very small segment of a chromosome had devastating effects on human development.
Multi-factorial inheritance: It is defined as one that is determined by a combination of factors, genetic and possibly also non-genetic, each with only a minor effect. Many common birth defects and various common disorders of midlife are ascribed to multifactorial inheritance.
Acquired somatic genetic disease: Not all genetic errors are present from conception. During each mitosis there is an opportunity for both single gene mutations to occur, because of DNA copy errors, and for numerical chromosome abnormalities to arise as a result of errors in chromosome 2separation, e.g., accumulating somatic mutations and chromosome abnormalities are now known to play a major role in causing cancer.
Each chromosome consists of two strands called as chromatids. These chromatids are joined at a primary constriction known as the centromere. Each centromere divides the chromosome into short and long arms designed p (= petite) and q (‘g’ = grande) respectively.
Morphologically, chromosomes (Fig. 1.1) are classified according to the position of the centromere. If this is located centrally, the chromosome is metacentric, if terminal it is acrocentric, and if the centromere is in an intermediate position the chromosome is submetacentric. Acrocenteric chromosomes sometimes have stalk-like appendages called satellites which form the nucleolus of the resting interphase cell.
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Fig. 1.1: Showing morphology of chromosomes
Karyotyping: The chromosomal constitution of an individual is called as karyotyping. The human karyotype for the male is 44+XY and that for the female is 44+XX. Circulating lymphocytes from the peripheral blood, skin, bone marrow, chorionic villi or cells from amniotic fluid can be used for karyotyping.
Chromosome banding: A number of techniques demonstrate the banded appearance of chromosomes. Special banding techniques are used to produce a restricted staining of one on the other subset of bands. Following are the various staining methods utilized to identify individual chromosomes.
G (Giemsa) banding
Q (Quinacrine) banding
R (Reverse) banding
C (Centrometric heterochromatin) banding High resolution banding
Karyotype analysis: It detects the number of chromosomes present in a specified number of cells, followed by careful analysis of the banding pattern of each individual chromosome in selected cells. Usually, the total chromosome count is determined in 10 to 15 cells, but if mosaicism is suspected then 30 or more cell counts will be undertaken.
Chromosome nomenclature: A given point on a chromosome is designated by the chromosome number, the arm (p or q), the region and the band, e.g., 11 p 12 would be referred to simply as band 12 on the short arm of chromosome 11. 2-q, 2,1 would mean band number 1 in the second region of the long arm of chromosome 2.
Table 1.1   Symbols used in describing a karyotype
Short arm
Long arm
Deletion, e. g., 46, XX, del (1) (q21)
Derivative of chromosome
Duplication, e.g., 46, XY, dup, (13) (q14)
Fragile site
Isochromosome, e.g., 46,X, I (Xq)
Inversion, e.g., 46 XX, inv (9) (p12q12)
In situ hybridisation
Ring, e.g., 46 XX, r (21)
Translocation, e.g., 46, XY, t (2;4) (q21;q21)
Reciprocal translocation
Robertsonian translocation
Tandem translocation
Terminal or end, i.e. tip of arm, e.g., pter or qter
Mosaicism, e.g., 46, XY/47, XXY
from → to
+ OR -
Sometimes used after a chromosome arm in text to indicate gain or loss of part of that chromosome, e.g., 46, XX, 5Q
A human zygote consists of a single cell at conception which undergoes rapid cell division to form mature human adult. This process of somatic cell division along with that of nucleus is called as mitosis. Mitosis comprises of 5 stages, viz, prophase, prometaphase, metaphase, anaphase and telophase.
The period between successive mitoses is known as the interphase of the cell cycle.
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Fig. 1.2: Stages of the cell cycle
Meiosis: It is the process of nuclear division which occurs during the final stage of gamete formation. It achieves two major objectives. Firstly, it facilitates halving of the diploid number of chromosomes so that each child receives half of its chromosome complement from each parent. Secondly, it provides an extraordinary potential for generating genetic diversity.
Abnormal chromosomes are the vehicles of inherited abnormalities. These are divided into numerical and structural, with a third category consisting of different chromosome constitutions in two or more cell lines.
Numerical abnormalities: It may occur during mitosis or meiosis. Abnormal chromosome number result almost invariably from the phenomenon of non-disjunction during the first and/or the second meiotic divisions. For example Down's syndrome, Turner's syndrome, Klinefelter's syndrome.
The causes of chromosomal aberrations are not precisely known. However, it is observed that certain factors predispose to such aberrations. These include ionizing radiations, viruses, chemical carcinogens, late maternal or paternal age, and possibly a few specific genes themselves.
Structural abnormalities: Structural abnormalities result from single or multiple breaks along the chromosomal length. The broken fragments are then either deleted or rearranged in various ways or shifted (translocated) to other chromosomes. Such “chromosomal mutations” may occur spontaneously i.e. without an apparent cause, or are triggered by external agents e.g., ionizing radiation or some drugs. Carriers of balanced rearrangement are at risk of producing children with an unbalanced complement. Chromosomal rearrangement is called as unbalanced when chromosomal complement contains an incorrect amount of chromosome material and the clinical effects are usually very serious.
  1. Translocations: It refers to the transfer of genetic material from one chromosome to another. It is of two types as follows;
Reciprocal translocation: It refers to breakage of at least two chromosomes with an exchange of the fragments. The incidence of reciprocal translocation in the general population is 1 in 500. The risk of a carrier of a balanced translocation in the birth of an abnormal baby is 1 to 10 percent.
Robertsonian translocation: Robertsonian translocation results from breakage of two acrocentric chromosomes at or close to their centromeres, with subsequent fusion of their long arms.4
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Fig. 1.3: Types of translocations
  1. Deletion: Deletion is the loss of part of a chromosome and results in monosomy for that segment of the chromosome. Deletion of part of a chromosome is often referred to as partial monosomy. Any deletion resulting in loss of more than 2 percent of the total haploid genome will have a lethal outcome. For example Turner's syndrome is an XO condition resulting from the deletion of a whole chromosome, Cri-du-chat syndrome in which part of the short arm of chromosome is deleted, Prader-Willi syndrome, Angelman syndrome.
  2. Insertion: It refers to insertion of segment of one chromosome into another chromosome. It can result in either balanced or unbalanced chromosome complement.
  3. Inversion: An inversion refers to two-block rearrangement involving a single chromosome in which a segment is reversed in position i.e. inverted. If it involves a centromere, it is called as pericentric inversion. If it involves only one arm of the chromosome, it is known as paracentric inversion. If there is no loss or gain of genetic material, there may be no significant clinical manifestations.
  4. Ring chromosome : These are formed when a break occurs on each arm of a chromosome leaving two “sticky” ends on the central position which reunite as a ring. The consequences will depend on the length and the role of the genetic material lost. Ring chromosomes have been found in every chromosome group. Many of these are not associated with consistent group, except that mental retardation is a consistent feature.
  5. Isochromosomes: It shows loss of one arm with duplication of the other. Each chromosome, thus has excess of some genetic material and deficiency of some other genetic material. It accounts for approximately 15 percent of all other cases of Turner's syndrome.
If the non-disjunction occurs after a few mitotic division have already occurred, more than two cell lines which differ in their genetic constitution but are derived from a single zygote may be observed. Some will have normal and the others will have abnormal complement of chromosomes. Mosaicism accounts for 1-2 percent of all clinically recognized cases of Down's syndrome.
Chimera means a Greek monster which had the head of a lion, the body of a goat and the tail of a dragon. It is defined as the presence in an individual of two or more genetically distinct cell lines derived from more than one zygote, i.e. they have a different genetic origin.5
Table 1.2   Symbols commonly used in pedigree charts
Unaffected male
Affected female
Sex unspecified
Number of children of sex indicated
Dizygotic twins
Monozygotic twins
Propositus (i.e. the affected individuals who brought the fly to the attention of the genicist)
Carrier of sex linked recessive
Consanguineous mating
An important reason for studying the pattern of inheritance of disorders is to understand the different ways in which genes are handed down from one generation to another or study its frequency among relatives to understand its genetics.
An inherited trait may depend on a single gene pair, called as Mendelian inheritance or on the cumulative effect of a large number of genes, called as polygenic inheritance. Mendelian inheritance may be either autosomal or sex linked. In autosomal traits, the genes are located on any of the 22 pairs of autosomes and in sex linked traits, the genes belong to the X or Y chromosome. Very rarely when neither parent is affected, spontaneous mutation in the gamete is the likely cause.
When the two members of an allelic pair are identical, they are said to be homozygous and when they are unlike each other, the combination is called as heterozygous. A trait constitutes the phenotype whereas the allelic pair constituting the trait constitutes genotype for that trait.
Autosomal dominant trait is the one which manifests in the heterozygous state i.e., in a person possessing both an abnormal or mutant allele and the normal allele. It is often due to mutation in a gene coding for a structural protein and possible to trace a dominantly inherited trait or disorder through many generations of a family. For example porphyria, brachydactyly, osteogenesis imperfecta. This is sometimes referred to as ‘vertical’ transmission.
Genetic Risk
Any child with an autosomal dominant disorder has a 50 percent chance of passing on the mutant gene to offspring. Thus, each child of an affected individual has a 50 percent chance of being affected.
  1. Trait expressed in both homozygous and heterozygous states.
  2. Occurrence and transmission not influenced by sex.
  3. 6Trait transmitted by an affected person if heterozygous to half his/her children on an average and if homozygous to all his/her children.
  4. Trait seen in every generation.
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Fig. 1.4: Punnett's square showing possible gamete combinations for an autosomal dominant allele
Each gene has only one primary effect in that it directs the synthesis of a polypeptide chain. From this primary effect, many different consequences may arise. Multiple phenotypic effects produced by a single mutant gene or gene pair are examples of pleiotropism. For example tuberous sclerosis.
Penetrance and Expressivity
Penetrance applies to a gene's likelihood of being expressed at all; expressivity refers to the degree of expression, i.e. whether clinically the condition is expressed in a mild, moderate or severe form.
Variable Expressivity
It refers to variations in clinical features of autosomal disorders seen from person to person. For example neurofibromatosis Type I.
Reduced Penetrance
An individual heterozygous for a dominant mutation, but has no features of the disorder is said to represent non-penetrance. In individuals heterozygous for autosomal disorders, if the presence of the mutation remains undetected clinically, it is called as reduced penetrance.
Forme Fruste
This is any mild clinically insignificant expression of a genetic trait in an abnormality, disease or syndrome. For example Marfan's syndrome.
The sudden unexpected appearance of a condition arising as a result of a mistake occurring in the transmission of a gene is called as new mutation. This explains a trait appearing in an individual in one generation when no one else in previous generations has been affected. For example achondroplasia. When a mutation does not have any effect on the health of an individual, it is called as polymorphism. A mutation may occur due to a change of a base sequence on the exon or functioning part of the gene. This may result in formation of an altered protein with different amino acid constitution and is called as nissence mutation. Other forms of mutation are due to change in splicing efficiency of RNA, deletion or addition of DNA. This may result in formation of smaller amount of protein or even its total absence. A mutation may alter regulatory function of the gene, resulting in unrestricted growth or malignancy.
Codominance and Intermediate Inheritance
Codominance refers to two allelic traits which are both expressed in the heterozygous state. For example, the ABO blood group. If a heterozygote is different from both homozygotes, the genes concerned are said to show intermediate inheritance. For example Sickle cell anemia.
Recessive traits and disorders are only manifest when the mutant allele is present in a double dose, i.e. homozygosity. Individuals heterozygous for a recessive mutant allele show no features of the disorder and are perfectly healthy, i.e. they are carriers.
7In clinical medicine, parental consanguinity is a strong clue, though not a proof, that a disorder is autosomal recessive. Even if parents consider themselves unrelated, they may have common ancestry within the last few generations. For example cystic fibrosis, alkaptonuria.
Genetic Risks
Various combinations resulting from these traits are that the offspring of two heterozygotes have a 1 in 4 (25%) chance of being homozygous affected, a 1 in 2 (50%) chance of being heterozygous unaffected and a 1 in 4 (25%) chance of being homozygous unaffected.
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Fig. 1.5: Punnett's square showing possible gamete combinations for heterozygous carrier parents of an autosomal recessive allele
  1. Trait expressed only in homozygous state.
  2. Occurrence and transmission not influenced by sex.
  3. Seen only in sibs – brothers and sisters. Not seen in the parents, off-springs or other relatives.
  4. Ratio of affected, carrier, and non-affected is 1:2:1 in sibs; the recurrence risk in such a family is 1 in 4 for each birth.
  5. Parents of affected child may be related consanguineously (cousin marriage).
If an individual who is homozygous for an autosomal recessive disorder marries a carrier of the same disorder, their children have a 1 in 2 (50%) chance of being affected.
Locus Heterogeneity
A disorder inherited in the same manner can be due to mutations in more than one gene, or what is known as locus heterogeneity. For example sensorineural hearing impairment.
Mutational Heterogeneity
Heterogeneity also occurs at the allelic level. Individuals with two different mutations at the same locus are known as compound heterozygotes, thus constituting allelic or mutational heterogeneity.
Sex Linked Inheritance
Sex linked inheritance refers to the pattern of inheritance shown by the genes which are located on either of the sex chromosomes. Genes carried on X chromosome are referred as X-linked, e.g. hemophilia, partial color blindness, vitamin D resistant rickets, whereas genes carried on Y chromosome are referred to as Y linked inheritance, e.g. hairy pinna.
X-linked inheritance trait is the one determined by a gene carried on the X chromosome and it manifests in males. Diseases inherited in an X-linked manner are transmitted by healthy heterozygous. Female carriers to affected males, as well as by affected males to their obligate carrier daughters with a consequent risk to male grandchildren through these daughters. This is also referred to as diagonal pattern of transmission. For example hemophilia.
Genetic Risks
A male transmits his X-chromosomes to each of its daughters, thus making them obligate carriers and his X-chromosome to each of his sons. For a carrier female of an X-linked recessive disorder having children with a normal male, each son 8has a 1 in 2 (50%) chance of being affected and each daughter has a 1 in 2 (50%) chance of being a carrier.
In several X-linked disorders heterozygous female exhibit a mosaic phenotype with a mixture of features of the normal and mutant alleles. This mosaic pattern can be explained through the random process of X inactivation.
  1. Always expressed by all members.
  2. Females affected only if homozygous.
  3. Affected male does not transmit to his sons, transmits to all his daughters.
  4. Carrier female transmits to 50 percent of her children –both male and female.
  5. Trait not transmitted from male to male.
  6. Trait transmitted from affected man through all his daughters to half of all his grandsons.
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Fig. 1.6: Punnett's square showing possible gamete combinations for the offspring of a male affected by an X-linked recessive disorder
X-Linked Dominant Inheritance
Disorders with X-linked dominant inheritance are uncommon and manifest in the heterozygous female as well as in the male who has the mutant allele on his single X chromosome. With this inheritance, both daughters and sons of an affected female have a 1 in 2 (50%) chance of being affected. However, an affected male transmits the trait to all his daughters but to none of his sons. For example vitamin D resistant rickets.
  1. In female, trait manifests in homozygous as well as in heterozygous state.
  2. Homozygous female will transmit trait to all the children.
  3. Always expressed in male who transmits to all his daughters but to none of his sons.
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Fig. 1.7: Punnett's square showing possible gamete combination for the offspring of a female carrier of an X-linked dominant disorder
Y-Linked Inheritance
This implies that only males are affected. An affected male transmits Y-linked traits to all his sons but to none of his daughters. For example Hairy ears, webbed toes.
  1. Males only get affected.
  2. Affected male transmits the trait to all his sons but to none of his daughters.
Non-mendelian Inheritance
These are number of different mechanisms recognized to explain certain disorders which do not follow classical patterns of Mendelian inheritance.
  1. 9Anticipation: In some autosomal dominant traits or disorders, such as myotonic dystrophy, the onset of the disease occurs at an earlier age in the offspring than in the parents or the disease occurs with increasing severity in subsequent generations. This phenomenon is called as anticipation. For example Huntington's chorea, myotonic dystrophy.
  2. Mosaicism: An individual, or a particular tissue of the body, can consist of more than one cell type or line, through an error occurring during mitosis at any stage after conception, or what is known as mosaicism. It can be seen in somatic cells or germ cells as well.
    1. Somatic mosaicism: This explains features of a single gene disorder being less severe in an individual than usual or by being confined to a particular part of the body in a segmental distribution. For example neurofibromatosis Type I.
    2. Gonadal mosaicism: Germ line or gonadal mosaicism is characterized by phenotypically normal parents, all investigations or genetic tests being normal but more than one of these parents being affected. For example osteogenesis imperfecta.
  3. Uniparental disomy: It is characterized by inheritance of both homologous of a chromosome pair from only one of their parents as against each parent which is normally observed.
  4. Genomic imprinting: Depending on whether a gene is inherited from the father or from the mother, different clinical features may manifest which is called as genomic imprinting as against the original belief that genes on homologous chromosomes were expressed equally. For example Prader Willi syndrome, Angelman syndrome.
Cells with high energy requirements such as brain and muscle have more than copies of mitochondrial DNA. Mitochondria are inherited from the mother through oocyte. Mitochondrial DNA has a higher rate of spontaneous mutation than nuclear DNA and the accumulation of mutations in mitochondrial DNA has been proposed as being responsible for some of the somatic effects seen with aging.
Cytoplasmic or mitochondrial inheritance is observed in some rare disorders which affect both males and females but are transmitted only through females, so called maternal or matrilineal inheritance. It provides explanation to certain rare disorders characterized by muscle and neurological features with diabetes and deafness. As mitochondria have an important role in cellular metabolism, it is not surprising that the organs most susceptible to mitochondrial mutations are the central nervous system, skeletal muscle and heart. For example Leigh disease, mitochondrial encephalopathy-lactic acidosis and stroke-like syndrome (MELAS).
  1. Emery's Elements of Medical Genetics – 11th edition, Robert F. Muller. Ian D Young The history and impact of genetics in medicine Chromosome and cell division Patterns of inheritance Polygenic and multi-factorial inheritance
  1. Essential Pediatrics – O.P. Ghai
  1. Genetics in Medicine – 4th edition, 1986, Thompson and Thompson. 
  1. Human cytogenetics, volume 1, New York
  1. Human chromosomes: Structure, behavior, effects: Cytogenet Cell Genet
  1. Molecular structure of human chromosome: Cytogenet Cell Genet
  1. Textbook of Pediatrics, 15th edn., Richard E. Behrman, Robert M. Kliegman, Ann M. Arvin.
  1. The chromosomal basis of human neoplasia: Cytogenet Cell Genet
Genetics: The study of inherited traits and their transmission from generation to generation.
10Mendel (1866): Through hid garden-pea experiments laid the foundation for a scientific study of this discipline. His laws of ‘segregation’ and ‘random or independent assortment’ are a laid by-word in genetics.
Cytogenetics: The science that combines the methods and findings of cytology and genetics, concerned mainly with the chromosomes and their co-relations with the phenotype.
Alleles: One or more alternative forms of a gene found at the same locus on homologous chromosomes in an indivisual and/or in a population of indivisuals. Alleles segregate at meiosis; a child thus, usually receives only one of each pair of alleles from each parent.
Chromosomes: Organelles found in pairs in the eukaryotic nuclei, have a species-specific number and during gamete formation by meiosis, get redistributed in them so that each member of a pair is represented. Fertilization restores the species-specific paired number, which for man is 46 or 23 pairs. Twenty-two of these pairs are autosomes and the remaining pair, the sex chromosomes, are designated X and Y, because of their dissimilarity and their role in sex determination.
Karyotype: This is the chromosome formula for a cell or an indivisual, female karyotype being 44+XX and male 44+XY.
Classification of chromosomes: They are classified and numbered on the basis of their decreasing length and position of their centromeres.
Centromere: The small mass of heterochromatin within a chromosome by which the chromatids are held together, and by which a chromosome becomes attached to the spindle during cell division.
Chromosome structure: Each chromosome is a supercoiled package of DNA and several proteins. Progressive anatomization of a chromosome reveals it to be made of chromomeres, each chromomere made up of coils of chromatin fiber, each chromatin fiber is made of smaller units, the nucleosomes, each nucleosome comprising of DNA and histones.
Abnormal chromosomes: Chromosomes may be abnormal either in number or in structure.
Numerical abnormalities are ‘euploid’ when exact multiples of a chromosome set occur in a cell, or ‘aneuploid’ when one or more chromosome is more or less than the set.
Structural abnormalities are:
  1. Deletion: The elimination of a part of chromosome following a chromosomal break.
  2. Ring chromosome: Following terminal breaks, the chromosomal ends join each other.
  3. Translocation: This occurs due to breaks in two homologous chromosomes and the attachment of broken pieces to the wrong chromosome. A mutual ‘wrong’ exchange is called reciprocal translocation.
  4. Isochromosome: A duplication-deletion anomaly due to a tranverse split of a metaphase chromosome instead of a longitudinal one. Results in metacentric chromosomes in which their two limbs carry identical gene loci.
  5. Inversion: Following two breaks within a chromosome, the segment in between gets reversed and reattached in the same chromosome. The gene loci in the fragment get ‘inverted’ in sequence. An inversion may include the centromere – ‘pericentric’ or exclude it – ‘paracentric’.
  6. Duplication: The representation of a protion or a fragment of a chromosome more than twice in a zygote or more than once in a gamete. Usually occurs due to ‘unequal crossing over’ in meiosis. Can also occur during gametogenesis in a carrier of translocation, of inversion or of ring chromosome.
Gene: Made up of varying lengths of DNA.
Mutation: It is any sudden heritable structural change in DNA.
11Heterogeneity: Process in which an identical or similar phenotype is produced by a different genetic mechanism. Genocopy and genetic mimic are terms for a genetic trait which is phenotypically similar to, but fundamentally (genetically) distinct from another.
Single gene inheritance: Trait determined by genes at a single locus, such inheritance, from one generation to the next, follows Mendel's laws.
Heterozygote: An indivisual who possesses two different alleles at one particular locus on homologous chromosomes.
Autosomal dominant inheritance:
  • Trait expressed in both homozygous and heterozygous states.
  • Occurrence and transmission not influenced by sex.
  • Trait transmitted by an affected person if heterozygous to half his/her children on an average and if homozygous to all his/her children.
  • Trait seen in every generation.
Autosomal recessive inheritance:
  • Trait expressed only in homozygous state.
  • Occurrence and transmission not influenced by sex.
  • Seen only in sibs – brothers and sisters. Not seen in the parents, off-springs or other relatives.
  • Ratio of affected, carrier, and non-affected is 1:2:1 in sibs; the recurrence risk in such a family is 1 in 4 for each birth.
  • Parents of affected child may be related consanguineously (cousin marriage).
Codominance: Phenomenon of both the alleles of a pair expressing fully in the heterozygote. Codominant gene and trait are the gene involved and the concerned trait in codominant inheritance.
Intermediate inheritance: Phenomenon where a heterozygote is neither like a homozygote with both the dominant genes nor like a homozygote with both the recessive genes.
Sex-linked inheritance: Sex chromosome X-linked and sex chromosome Y-linked.
X-linked inheritance:
  1. No inheritance from father to son.
  2. Father always transmits gene to daughter.
A. X-linked recessive inheritance:
  • Always expressed by all members.
  • Females affected only if homozygous.
  • Affected male does not transmit to his sons, transmits to all his daughters.
  • Carrier female transmits to 50 percent of her children—both male and female.
  • Trait not transmitted from male to male.
  • Trait transmitted from affected man through all his daughters to half of all his grandsons.
B. X-linked dominant inheritance:
  • In female, trait manifests in homozygous as well as in heterozygous state.
  • Homozygous female will transmit trait to all the children.
  • Always expressed in male who transmits to all his daughters but to none of his sons.
Y-linked inheritance or holandric inheritance:
  • Males only get affected.
  • Affected male transmits the trait to all his sons but to none of his daughters.
Variation in the expression of genes:
  1. Penetrance: Ability of a gene to express phenotypically.
  2. Nonpenetrance: Inability of a gene to express phenotypically.
  3. Expressivity: The varying degree of phenotypic expression of an abnormal gene, i.e., mild, moderate, severe.
  4. Forme fruste: Mild, clinically insignificant expression of a genetic trait in an abnormality, disease or syndrome.
Pleiotropy: A number of distinct and seemingly unrelated phenotypic effects from a single gene abnormality. Usually, because the gene concerned directs the synthesis of a polypeptide chain which has wide spreads role in maintaining the structure and function of the body.
12Association: Occurrence of two or more phenotypic characters in a given population in a frequency greater than would be expected on the basis of chance.
Linkage: Phenomenon where two genes located close together on a chromosome do not assort independently of each other (as expected from Mendel's law of independent assortment) during meiosis, but are transmitted to the same gamete more than 50 percent of times.
Recombination is the occurrence of progeny with combination of genes other than those that occurred in the parents. Recombination occurs because of independent assortment or crossing over.
Sex-linked traits: Genes though located on autosomes are expressed in only one sex e.g., primary sexual characters, differing in males and females.
Polygenic inheritance: Phenomenon of a trait being governed by a number of genes, each contributing a minor effect in expression of that trait. Trait shows a continuous variation i.e., quantitative variation in its manifestation in a population. This can be graphically shown as Gaussian, bell=shaped or normal curve – e.g., human height, pulse rate, blood pressure, blood cholesterol.
Multifactorial inheritance: Multiple genetic and non-genetic factors involved in determining the trait.
Quasicontinuous trait: Polygenic trait continuously distributed dependent on a threshold effect for manifestation. Basis of developmental defects.