Principles of Inheritance and Variation — NEET notes

Mendel's Laws of Inheritance

Gregor Mendel (1822–1884), an Austrian monk, discovered the fundamental laws of inheritance by studying seven contrasting traits in garden pea (Pisum sativum). His three laws — Dominance, Segregation, and Independent Assortment — form the foundation of classical genetics.

Law of Segregation: alleles separate during gamete formation each gamete gets ONE allele

Mendel's Experimental Design

Mendel chose Pisum sativum for specific reasons: short life cycle, contrasting traits, self-pollination (pure lines), and easy cross-pollination by emasculation.

Gregor Johann Mendel was an Augustinian monk who conducted hybridization experiments on garden pea (Pisum sativum) from 1856–1863 in his monastery garden in Brno. He studied seven pairs of contrasting traits and analyzed results mathematically — something no biologist had done before.

• Why pea? — Many contrasting traits, short generation time, self-pollinating (gives pure lines), easy to cross-pollinate artificially
• Pea flowers are bisexual — both male (stamens) and female (pistil) in same flower
• Emasculation — removing anthers from a bisexual flower before pollen matures, to prevent self-pollination
• 7 contrasting traits: stem height (tall/dwarf), flower colour (violet/white), flower position (axial/terminal), pod shape (inflated/constricted), pod colour (green/yellow), seed shape (round/wrinkled), seed colour (yellow/green)
• Mendel called the trait that appeared in F1 the dominant trait; the hidden one was recessive

Law of Dominance

When two organisms with contrasting traits are crossed, only one trait (dominant) appears in the F1 generation. The other trait (recessive) is masked but not lost.

The Law of Dominance states: when two parents differing in a pair of contrasting traits are crossed, the F1 hybrid shows only one of the two parental traits — the dominant trait. The other trait (recessive) remains hidden but reappears in F2.

• Characters are controlled by discrete units called factors (now called genes)
• Factors occur in pairs — one from each parent
• In a dissimilar pair (Tt), only the dominant factor (T) expresses itself
• The Law of Dominance is NOT universally valid — exceptions include incomplete dominance and codominance
• This law explains the phenotypic ratio of the monohybrid cross (3:1), not the genotypic ratio

Law of Segregation

During gamete formation, the two alleles of a gene separate (segregate) from each other so that each gamete receives only ONE allele. Also called the Law of Purity of Gametes.

The Law of Segregation (Mendel's First Law) states: the two alleles of a gene in a diploid organism separate during gamete formation, so each gamete carries only one allele for each trait. When gametes fuse at fertilization, the allele pair is restored.

Tt meiosis 1 2 T + 1 2 t (each gamete gets ONE allele)

• This is the most fundamental of Mendel's laws — universally valid with almost no exceptions
• Physical basis: homologous chromosomes separate during Anaphase I of meiosis
• Each gamete gets one allele from each gene → gamete is haploid (n)
• At fertilization, two haploid gametes fuse → diploid zygote (2n) with allele pair restored
• This law explains why the F2 ratio shows reappearance of recessive trait (1/4 = tt)

Law of Independent Assortment

When two pairs of contrasting traits are considered simultaneously, the factors for each trait assort independently of the factors for other traits during gamete formation.

The Law of Independent Assortment (Mendel's Second Law) states: when two or more pairs of genes are inherited simultaneously, the alleles of one gene assort independently of the alleles of another gene during gamete formation. This produces new combinations not present in either parent.

RrYy arrow gametes: RY, Ry, rY, ry (all 4 equally likely)

• Physical basis: random orientation of bivalents (homologous pairs) at the metaphase plate during Metaphase I of meiosis
• This law applies only to genes on different (non-homologous) chromosomes
• Genes on the same chromosome (linked genes) do NOT assort independently — they violate this law
• This law explains the 9:3:3:1 ratio in a dihybrid cross
• The 'new combinations' (recombinants) like RrYy producing Ry and rY gametes — this is the source of genetic variation

Monohybrid Cross

A cross between two parents differing in a single pair of contrasting traits. Mendel's monohybrid cross with tall (TT) and dwarf (tt) pea plants gave a 3:1 phenotypic ratio and 1:2:1 genotypic ratio in F2, establishing the concept of dominance and segregation.

F2 Phenotypic ratio = 3 (dominant) : 1 (recessive)

Monohybrid Cross Setup

A monohybrid cross involves parents homozygous for contrasting forms of a SINGLE trait. The F1 are all heterozygous and show the dominant phenotype. F2 shows the famous 3:1 ratio.

Mendel crossed true-breeding tall plants (TT) with true-breeding dwarf plants (tt). ALL F1 plants were tall — the dwarf trait disappeared completely. When F1 plants were self-pollinated, the F2 generation showed 3 tall : 1 dwarf.

P: TT tt arrow F_1: Tt (all tall) arrow F_2: TT : 2Tt : tt (3:1)

• F1 generation: ALL heterozygous (Tt), ALL show dominant phenotype (tall)
• F2 genotypic ratio: 1 TT : 2 Tt : 1 tt (1:2:1)
• F2 phenotypic ratio: 3 Tall : 1 Dwarf (3:1)
• The reappearance of dwarf in F2 proves that the recessive allele was NOT destroyed in F1 — just hidden
• True-breeding = homozygous (TT or tt); breeds true on self-pollination for several generations

Punnett Square

A grid method to predict genotypic and phenotypic ratios by listing all possible gamete combinations from both parents.

A Punnett square is a simple grid that shows ALL possible offspring genotypes from a cross. Each parent's gamete types go on one axis. Each cell shows the genotype from combining those two gametes.

• Punnett square for Tt × Tt: columns = T, t (from one parent); rows = T, t (from other parent)
• Cells: TT, Tt, Tt, tt → Genotypic ratio = 1 TT : 2 Tt : 1 tt
• Each cell has equal probability = 1/4
• The square works because of the Law of Segregation — each parent contributes one allele randomly

Test Cross & Back Cross

A test cross (crossing with homozygous recessive) reveals whether a dominant-phenotype individual is homozygous (TT) or heterozygous (Tt). A back cross is crossing F1 with either parent.

A tall pea plant could be TT or Tt — both look the same. To find out, cross it with a homozygous recessive (tt). This is called a test cross because it 'tests' the unknown genotype.

If TT tt arrow ALL Tt (all tall) | If Tt tt arrow 1 2 Tt + 1 2 tt (1:1)

• Test cross offspring ALL dominant → unknown parent is homozygous dominant (TT)
• Test cross offspring 1:1 (dominant : recessive) → unknown parent is heterozygous (Tt)
• Every test cross IS a back cross (crossing F1 with recessive parent), but a back cross with the DOMINANT parent is NOT a test cross
• Test cross is the standard experimental method to confirm genotype in genetics

Dihybrid Cross & Epistasis

A dihybrid cross tracks two pairs of contrasting traits simultaneously. Mendel's cross of round-yellow (RRYY) × wrinkled-green (rryy) gave a 9:3:3:1 ratio in F2, confirming independent assortment. Deviations from 9:3:3:1 arise due to gene interactions like epistasis.

F2 ratio = 9:3:3:1 (for two independently assorting genes with complete dominance)

Dihybrid Cross

When RrYy is selfed, each parent produces 4 gamete types (RY, Ry, rY, ry), giving a 4×4 = 16-cell Punnett square with the iconic 9:3:3:1 phenotypic ratio.

Mendel crossed round-yellow (RRYY) with wrinkled-green (rryy) pea seeds. F1 was all round-yellow (RrYy). On selfing F1, the F2 showed: 9 round-yellow : 3 round-green : 3 wrinkled-yellow : 1 wrinkled-green.

P: RRYY rryy arrow F_1: RrYy arrow F_2: 9 R _Y _ : 3 R _yy : 3 rrY _ : 1 rryy

• F1: All RrYy (heterozygous for both genes), shows both dominant traits
• F2 phenotypic ratio: 9:3:3:1 (requires 16-cell Punnett square)
• F2 genotypic ratio: 9 different genotypes in ratio 1:2:1:2:4:2:1:2:1
• New combinations (recombinants): round-green and wrinkled-yellow — these don't exist in either parent
• The 9:3:3:1 ratio = (3:1) × (3:1) — each gene segregates independently, confirming the Law of Independent Assortment

Epistasis

Epistasis is the interaction between genes at DIFFERENT loci where one gene masks or modifies the expression of another. This produces modified dihybrid ratios that deviate from 9:3:3:1.

Epistasis (epi = upon, stasis = standing) occurs when an allele at one locus masks/suppresses the expression of alleles at a DIFFERENT locus. The masking gene is epistatic; the masked gene is hypostatic. This modifies the classic 9:3:3:1 ratio.

• Complementary genes (9:7) — Both dominant alleles needed for phenotype. Example: flower colour in sweet pea. AABB/AaBb = coloured; A_bb, aaB_, aabb = all white
• Supplementary/Recessive epistasis (9:3:4) — Homozygous recessive at one locus masks the other. Example: coat colour in mice (agouti/black/albino)
• Dominant epistasis (12:3:1) — Dominant allele at one locus is epistatic to the other locus. Example: fruit colour in squash
• Duplicate genes (15:1) — Either dominant allele can produce the phenotype. Example: kernel shape in wheat
• Inhibitory genes (13:3) — Dominant allele at one locus inhibits expression of dominant allele at another locus

Dihybrid Test Cross

Crossing a dihybrid heterozygote (RrYy) with a double homozygous recessive (rryy) gives a 1:1:1:1 ratio if genes assort independently.

The dihybrid test cross is RrYy × rryy. Since the recessive parent (rryy) can only contribute ry gametes, the offspring directly reflect the gamete types of the heterozygous parent.

RrYy rryy arrow RrYy : Rryy : rrYy : rryy = 1:1:1:1

• If the ratio is 1:1:1:1 → genes are on different chromosomes (independent assortment confirmed)
• If the ratio deviates from 1:1:1:1 (more parental types, fewer recombinants) → genes are linked (on the same chromosome)
• This test cross is the classic method to detect linkage
• Mendel always got 1:1:1:1 because his 7 genes happened to be unlinked

Incomplete Dominance & Codominance

Not all gene pairs follow Mendel's law of dominance perfectly. In incomplete dominance, the heterozygote shows a BLENDED intermediate phenotype (e.g., pink snapdragon). In codominance, BOTH alleles express simultaneously without blending (e.g., AB blood group). Both give a 1:2:1 F2 phenotypic ratio.

Incomplete dominance F2: 1 (dominant) : 2 (intermediate) : 1 (recessive)

Incomplete Dominance

In incomplete dominance, the dominant allele cannot fully mask the recessive allele. The heterozygote shows an INTERMEDIATE phenotype between the two homozygous parents.

In snapdragon (Antirrhinum), crossing a red-flowered (RR) plant with a white-flowered (rr) plant gives F1 with PINK flowers (Rr) — not red! Neither allele is completely dominant. On selfing F1, the F2 ratio is 1 Red : 2 Pink : 1 White.

RR (red) rr (white) arrow F_1: Rr (pink) arrow F_2: 1 RR : 2 Rr : 1 rr

• Phenotypic ratio = Genotypic ratio = 1:2:1 (unlike 3:1 in complete dominance)
• The heterozygote (Rr) has an intermediate/blended phenotype (pink = blend of red + white)
• This is NOT blending inheritance! F2 still shows pure red and pure white — alleles don't mix permanently
• The Law of Segregation still holds perfectly — only the Law of Dominance is modified
• Another example: 4 o'clock plant (Mirabilis jalapa) — same red × white → pink pattern

Codominance

In codominance, both alleles of a gene express themselves SIMULTANEOUSLY in the heterozygote. Neither is dominant over the other, and there is no blending — both phenotypes appear side by side.

In codominance, both alleles produce their OWN protein, and both proteins are fully functional and detectable. The heterozygote shows BOTH parental phenotypes simultaneously — not an intermediate blend.

• Best example: ABO blood groups — I^A I^B individuals express BOTH A and B antigens on RBC surface (blood group AB)
• Another example: Sickle cell trait (HbA HbS) — both normal (HbA) and sickle (HbS) haemoglobin are produced
• In codominance, both alleles are represented with capital superscript letters ( I^A , I^B ) because neither is 'lowercase recessive'
• Like incomplete dominance, phenotypic ratio = genotypic ratio = 1:2:1 in F2

Rh Factor

The Rh factor is determined by a separate gene from ABO. Rh+ (dominant) means Rh antigen is present on RBCs. Rh- (recessive) means it is absent. Critical during pregnancy (erythroblastosis foetalis).

The Rh factor (named after the Rhesus monkey where it was first discovered) is an antigen on the surface of RBCs. The Rh gene has two alleles: Rh+ (dominant) and Rh- (recessive). About 97% of Indians are Rh+.

• Rh+ genotypes: Rh^+ Rh^+ or Rh^+ Rh^- (both show Rh antigen on RBCs)
• Rh- genotype: Rh^- Rh^- only (no Rh antigen on RBCs)
• Rh factor follows simple Mendelian dominance — Rh+ is completely dominant over Rh-
• Erythroblastosis foetalis (Haemolytic Disease of Newborn): occurs when Rh- mother carries Rh+ foetus
• Mother's immune system makes anti-Rh antibodies during first pregnancy → these attack the Rh+ RBCs of the second Rh+ foetus
• Prevention: Rho-GAM injection (anti-Rh antibodies) given to Rh- mother within 72 hours of first delivery to prevent sensitization

Multiple Allelism & Pleiotropy

Multiple allelism occurs when a gene has MORE than two allelic forms in a population (though any individual still carries only two). ABO blood groups have three alleles: I^A, I^B, and i. Pleiotropy is the opposite: one gene affecting MULTIPLE phenotypic traits (e.g., sickle cell anaemia gene affects haemoglobin, spleen, kidneys, joints).

ABO alleles: I^A, I^B (codominant to each other), i (recessive to both)

ABO Blood Groups

The ABO blood group is determined by the gene I (Isoagglutinin) with three alleles: I^A, I^B, and i. I^A and I^B are codominant to each other but both are dominant over i.

The ABO blood group system is controlled by a single gene (I) with three alleles: I^A , I^B , and i . Since each person has only two copies of any gene, there are 6 possible genotypes but only 4 blood group phenotypes (A, B, AB, O).

• Blood Group A: genotype I^A I^A or I^A i → A antigen on RBCs, anti-B antibodies in plasma
• Blood Group B: genotype I^B I^B or I^B i → B antigen on RBCs, anti-A antibodies in plasma
• Blood Group AB: genotype I^A I^B → BOTH A and B antigens on RBCs, NO antibodies in plasma → universal acceptor
• Blood Group O: genotype ii → NO antigens on RBCs, BOTH anti-A and anti-B antibodies in plasma → universal donor
• I^A and I^B are codominant to each other (both express in AB), but both are dominant over i

Multiple Allelism

When a gene exists in more than two allelic forms in a population, it is called multiple allelism. Though a population has many alleles, each diploid individual still carries only TWO alleles.

A gene can mutate in different ways, producing more than two allelic forms. When three or more alleles of a gene exist in a population, it's called multiple allelism. But remember: any single individual is diploid and carries only two alleles.

• Multiple alleles arise by mutation of the same gene → different versions accumulate in the population
• ABO blood group: 3 alleles ( I^A, I^B, i ) in the population → 6 genotypes → 4 phenotypes
• Coat colour in rabbits: 4 alleles — C (full colour) > c^ ch (chinchilla) > c^h (Himalayan) > c (albino)
• A population can have many alleles, but an individual always has exactly two (one from each parent)
• Number of genotypes from n alleles: n(n+1) 2 (for 3 alleles → 6 genotypes)

Pleiotropy

Pleiotropy occurs when a single gene influences MULTIPLE apparently unrelated phenotypic traits. The sickle cell anaemia gene is the classic NCERT example.

Pleiotropy is the opposite of multiple allelism conceptually. Instead of many alleles → one trait, here ONE gene → many traits. A single gene mutation can have cascading effects on multiple organ systems.

• Sickle cell anaemia: a single point mutation in the -globin gene (GAG → GUG, Glu → Val at position 6) causes sickling of RBCs
• This ONE mutation affects: RBC shape (sickle), oxygen transport (reduced), spleen (damaged), kidneys, joints, lungs, brain (blocked capillaries)
• Phenylketonuria (PKU): mutation in the gene for phenylalanine hydroxylase → affects skin colour (fair), brain development (intellectual disability), urine composition (phenylpyruvic acid)
• Pleiotropy is very common — most genes are pleiotropic because gene products participate in multiple biochemical pathways
• Mendel's gene for seed shape in peas is also pleiotropic — affects seed shape AND starch grain shape

Sex Determination

Sex determination is the mechanism by which an organism develops as male or female. Different organisms use different systems: XX-XY (humans, Drosophila), XX-XO (grasshoppers), ZW-ZZ (birds, moths). In humans, the Y chromosome's SRY gene triggers male development. In honey bees, sex is determined by ploidy level (haplodiploidy).

Humans: XX = Female, XY = Male | Birds: ZW = Female, ZZ = Male

Sex Chromosomes vs Autosomes

Humans have 46 chromosomes: 22 pairs of autosomes (same in both sexes) and 1 pair of sex chromosomes (XX in females, XY in males). Only 1 out of 23 pairs determines sex.

In humans, out of 23 pairs of chromosomes: 22 pairs are autosomes (identical in males and females, determine body characteristics) and 1 pair is the sex chromosomes (different in males and females, determines sex). Females have XX, males have XY.

• Human female karyotype: 44 autosomes + XX (22 pairs autosomes + 1 pair X)
• Human male karyotype: 44 autosomes + XY (22 pairs autosomes + 1 X + 1 Y)
• The X chromosome is much larger than Y and carries ~800 genes
• The Y chromosome is the smallest human chromosome, carries ~50-60 genes
• The SRY gene (Sex-determining Region Y) on the Y chromosome produces TDF (Testis Determining Factor) — the master switch for male development

Different Systems

Nature has evolved multiple mechanisms for sex determination. The XX-XY system (humans, most mammals, Drosophila), XX-XO system (grasshoppers), ZW-ZZ system (birds, reptiles, moths), and haplodiploidy (honey bees) are the major ones.

Not all organisms determine sex the same way. Here are the four major chromosomal mechanisms of sex determination that NCERT describes:

• XX-XY system (humans, most mammals, *Drosophila*): Female = XX (homogametic), Male = XY (heterogametic). Male determines sex of offspring
• XX-XO system (grasshoppers, cockroaches): Female = XX, Male = X0 (only one sex chromosome, no Y). Male produces two types of sperm: X-bearing and no-sex-chromosome
• ZW-ZZ system (birds, some reptiles, moths, butterflies): Male = ZZ (homogametic), Female = ZW (heterogametic). FEMALE determines sex of offspring — reverse of humans!
• Haplodiploidy (honey bees, ants, wasps): Males are haploid (n) from unfertilized eggs (parthenogenesis), Females are diploid (2n) from fertilized eggs. No sex chromosomes involved!

Henking's X Body

In 1891, Henking observed that during spermatogenesis in a fire-wasp, a peculiar nuclear body moved to only one pole. He called it the X-body (later identified as the X chromosome). This was the first evidence of sex chromosomes.

In 1891, German scientist Henking studied spermatogenesis in the fire-wasp (*Pyrrhocoris*) and noticed that 50% of sperm received a peculiar darkly-staining nuclear body while the other 50% didn't. He called it the X-body — later identified as the X chromosome.

• Henking couldn't confirm whether X-body was a chromosome → called it 'X-body' (X for unknown)
• In the XX-XO system (grasshopper), 50% sperm have X and 50% have no sex chromosome
• Sperm with X + egg (X) → XX = female; Sperm without X + egg (X) → XO = male
• Male grasshoppers have an odd number of chromosomes (2n-1 = one X, no Y)
• This was later expanded to the XX-XY system when the Y chromosome was discovered

Sex-Linked Inheritance

Sex-linked genes are located on the sex chromosomes (X or Y). X-linked recessive traits (colour blindness, haemophilia) appear more frequently in males because males have only ONE X chromosome — no second X to mask the recessive allele. This is why haemophilia is called the 'royal disease' — it spread through Queen Victoria's descendants.

X^H X^h X^H Y arrow Carrier daughters (50%), Haemophilic sons (50%)

X-Linked Recessive Inheritance

X-linked recessive traits are expressed in males with just ONE copy of the recessive allele (hemizygous) because the Y chromosome has no corresponding allele. Females need TWO copies to express the trait — one on each X.

For an X-linked recessive trait: a male needs only ONE copy of the recessive allele (he's hemizygous — X^h Y ) to show the trait. A female needs TWO copies ( X^h X^h ) — if she has one normal allele ( X^H X^h ), she's a carrier (phenotypically normal, but can pass it to sons).

• Colour blindness: gene for red-green colour vision is on the X chromosome. Affects ~8% of males but only ~0.4% of females
• Haemophilia: gene for clotting factor VIII (Haemophilia A) or IX (Haemophilia B) is on X chromosome
• Males ALWAYS get their X from their MOTHER → X-linked traits pass from mother to son (criss-cross inheritance)
• Males NEVER get X-linked traits from their FATHER (father gives Y to son)
• An affected male ( X^h Y ) passes his X to ALL daughters → all daughters are at least carriers ( X^H X^h )
• A carrier female ( X^H X^h ) passes X^h to 50% of sons → 50% sons are affected

Colour Blindness Crosses

Understanding all possible crosses for colour blindness is essential for NEET. The key is tracking the X chromosome through generations.

Let X^C = normal vision allele (dominant), X^c = colour-blind allele (recessive). Here are the critical crosses:

• Carrier female × Normal male: X^C X^c X^C Y → Daughters: 50% normal ( X^C X^C ), 50% carrier ( X^C X^c ); Sons: 50% normal ( X^C Y ), 50% colour-blind ( X^c Y )
• Carrier female × Colour-blind male: X^C X^c X^c Y → Daughters: 50% carrier ( X^C X^c ), 50% colour-blind ( X^c X^c ); Sons: 50% normal ( X^C Y ), 50% colour-blind ( X^c Y )
• Normal female × Colour-blind male: X^C X^C X^c Y → ALL daughters carrier ( X^C X^c ), ALL sons normal ( X^C Y ) — 0% affected in this generation
• Colour-blind female × Normal male: X^c X^c X^C Y → ALL daughters carrier ( X^C X^c ), ALL sons colour-blind ( X^c Y )
• For a female to be colour-blind: father MUST be colour-blind AND mother must be at least a carrier

Y-Linked Inheritance & Barr Body

Y-linked (holandric) genes pass exclusively from father to ALL sons. Barr body formation (X-inactivation) in females is nature's way of equalizing X-linked gene dosage between XX females and XY males.

Y-linked (holandric) genes are on the Y chromosome and pass ONLY from father to son — never to daughters. Examples include the SRY gene and genes for hypertrichosis (excessive ear hair). Separately, X-inactivation (Lyon hypothesis) ensures that females don't get a 'double dose' of X-linked genes.

• Y-linked traits: pass from father to ALL sons (100%), never to daughters. Example: hypertrichosis (hairy ear pinna)
• Barr body: one of the two X chromosomes in female cells is randomly inactivated early in embryonic development → appears as a dark-staining body at the nuclear periphery
• Lyon hypothesis: the inactivated X is chosen randomly in each cell → females are genetic mosaics for X-linked genes
• Barr body count = number of X chromosomes - 1. Normal female (XX) = 1 Barr body. Normal male (XY) = 0 Barr bodies
• Dosage compensation: X-inactivation ensures males (1X) and females (effectively 1X active) have equal expression of X-linked genes

Genetic Disorders

Genetic disorders are caused by alterations in genes or chromosomes. Mendelian disorders follow single-gene inheritance patterns (sickle cell anaemia, thalassemia, PKU, cystic fibrosis, haemophilia, colour blindness). Chromosomal disorders involve changes in chromosome number or structure (Down syndrome/trisomy 21, Turner syndrome/45,XO, Klinefelter syndrome/47,XXY).

Aneuploidy: 2n 1 | Trisomy (2n+1), Monosomy (2n-1)

Mendelian Disorders

Mendelian disorders are caused by mutation in a single gene and follow Mendel's laws. They can be autosomal dominant, autosomal recessive, or sex-linked recessive. Most are autosomal recessive.

Mendelian disorders are caused by a mutation/alteration in a single gene. They follow simple inheritance patterns and can be predicted using pedigree analysis. These are also called single-gene disorders or monogenic disorders.

• Sickle Cell Anaemia: autosomal recessive, chromosome 11, Glu → Val substitution at position 6 of -globin chain (GAG → GUG in mRNA). Heterozygous carriers (HbA HbS) = sickle cell trait (mild/no symptoms, malaria resistance)
• Thalassemia: autosomal recessive. -thalassemia = reduced -globin chains (chr 16), -thalassemia = reduced -globin chains (chr 11). Leads to anaemia due to abnormal haemoglobin
• Phenylketonuria (PKU): autosomal recessive, chromosome 12. Deficiency of phenylalanine hydroxylase → phenylalanine accumulates → intellectual disability, fair skin
• Cystic Fibrosis: autosomal recessive, chromosome 7. Defective CFTR protein (chloride channel) → thick mucus in lungs, pancreas, digestive tract
• Haemophilia A: X-linked recessive. Deficiency of clotting factor VIII → prolonged bleeding. Mostly affects males

Chromosomal Disorders

Chromosomal disorders result from excess or loss of whole chromosomes (aneuploidy) or structural changes. They arise due to non-disjunction during cell division.

Chromosomal disorders are caused by absence or excess (or abnormal arrangement) of one or more chromosomes. The most common cause is non-disjunction — failure of homologous chromosomes (meiosis I) or sister chromatids (meiosis II) to separate properly during cell division.

• Aneuploidy: gain or loss of individual chromosomes. Trisomy (2n+1) = one extra chromosome. Monosomy (2n-1) = one missing chromosome
• Non-disjunction: failure of chromosomes to separate → one gamete gets an extra chromosome, the other loses one
• Down Syndrome (Trisomy 21): 47 chromosomes (2n+1 = 45+2). Extra copy of chromosome 21. Features: short stature, round face, broad forehead, intellectual disability, epicanthic fold, palm crease
• Turner Syndrome (45,XO): 45 chromosomes. Monosomy of X in females. Features: short stature, shield-shaped chest, webbed neck, ovaries absent/rudimentary, infertile
• Klinefelter Syndrome (47,XXY): 47 chromosomes. Trisomy of sex chromosomes in males. Features: tall, gynaecomastia (breast development), small testes, infertile, often has female-like features

Autosomal vs Sex-Linked Disorders

Autosomal disorders affect males and females equally. Sex-linked (especially X-linked recessive) disorders predominantly affect males because they have only one X chromosome.

Whether a disorder is autosomal or sex-linked determines WHO gets affected and HOW it passes through families. This is critical for pedigree analysis.

• Autosomal recessive: both parents are carriers (Aa × Aa) → 25% children affected, 50% carriers, 25% normal
• Autosomal dominant: one affected parent (Aa) × normal (aa) → 50% children affected. Example: polydactyly, Huntington's disease
• X-linked recessive: carrier mother ( X^H X^h ) × normal father ( X^H Y ) → 50% sons affected, 0% daughters affected (but 50% daughters are carriers)
• X-linked recessive traits often skip generations — affected grandfather → carrier daughter → affected grandson

Pedigree Analysis

Pedigree analysis is the study of a trait's inheritance pattern across multiple generations using a family tree diagram. It helps determine whether a trait is autosomal or sex-linked, dominant or recessive. Essential for genetic counselling and predicting the probability of a disorder in offspring.

If affected child from unaffected parents trait is RECESSIVE (parents are carriers)

Pedigree Symbols

Standard symbols are used universally in pedigree charts: squares for males, circles for females, filled shapes for affected individuals, horizontal lines for mating, vertical lines for offspring.

A pedigree is a diagram showing the inheritance of a trait through multiple generations of a family. It uses standardized symbols that every geneticist in the world reads the same way.

• Square = male; Circle = female
• Filled/shaded shape = affected individual; Empty shape = unaffected
• Half-filled = carrier (heterozygous, typically for autosomal recessive)
• Horizontal line connecting male and female = mating/marriage
• Vertical line going down = offspring; siblings shown on same horizontal level
• Roman numerals (I, II, III) = generation numbers; Arabic numerals (1, 2, 3) = individual numbers within a generation
• Double horizontal line = consanguineous mating (marriage between close relatives)

Identifying Inheritance Patterns

Systematically determine whether a trait is autosomal/X-linked and dominant/recessive by looking for specific clues in the pedigree.

When you see a pedigree on NEET, follow this systematic approach to identify the inheritance pattern:

• Step 1: Dominant or Recessive? — If TWO UNAFFECTED parents have an AFFECTED child → trait is RECESSIVE (both parents must be carriers Aa × Aa). If one AFFECTED parent has ALL affected children → likely DOMINANT
• Step 2: Autosomal or X-linked? — If affected FEMALES are present (especially with unaffected fathers) → likely AUTOSOMAL. If ONLY males are affected → suspect X-linked recessive
• Rule out X-linked recessive: An affected FATHER cannot have affected daughters (unless mother is carrier). If an affected father has an affected daughter → NOT X-linked recessive → autosomal recessive
• Autosomal dominant clues: trait appears in EVERY generation (no skipping), affected individuals have at least one affected parent, affects both sexes equally
• Autosomal recessive clues: trait SKIPS generations, unaffected parents can have affected children, affects both sexes equally, consanguinity increases risk
• X-linked recessive clues: predominantly MALES affected, trait skips generations, affected males get it from carrier mothers, no male-to-male transmission

Applications

Pedigree analysis is used in genetic counselling to calculate the probability of a child being affected. Understanding carrier status is critical for preventing genetic disorders in families.

Pedigree analysis has practical medical applications. Genetic counsellors use pedigrees to advise couples about the probability of their children inheriting genetic disorders.

• Genetic counselling: helps couples understand the risk of genetic disorders in their offspring
• If both parents are carriers (Aa × Aa) for an autosomal recessive disorder: 25% chance of affected child, 50% carriers, **25% normal
• Consanguineous marriages (between relatives) increase the risk of autosomal recessive disorders because both partners are more likely to carry the same rare recessive allele
• Prenatal diagnosis: amniocentesis or chorionic villus sampling can detect chromosomal disorders (Down syndrome) or specific gene mutations
• Pedigree analysis can also determine whether an unaffected individual is a carrier — critical for X-linked disorders

Quick recall

Both parents are carriers for sickle cell anaemia (Aa × Aa). What is the probability that their FIRST child is affected?

1/4 (25%). Each pregnancy is an independent event. The probability doesn't change based on previous children. Even if the first three children are normal, the fourth child still has a 1/4 chance of being affected.