# Principles of Inheritance β€” Part B (NEET Biology Class 12): Linkage, Sex Determination & Genetic Disorders Source: https://tracknation.in/story/principles-of-inheritance-part-b-neet-biology-class-12-linkage-sex-determination-genetic-disorders (TrackNation β€” free UPSC notes with PYQs) > NEET Class 12 Principles of Inheritance and Variation, Part B, mined from NCERT: the chromosomal theory of inheritance (why Mendel was ignored, the 1900 rediscovery, Sutton and Boveri, Morgan's Drosophila work), linkage and recombination with Sturtevant's genetic maps, all four sex-determination systems (XO, XY, ZW, haplodiploid) in a comparison table plus humans and honey bees, mutation (point, frame-shift, mutagens), pedigree analysis, a full Mendelian disorders table (colour blindness, haemop ## Chromosomal Theory, Linkage & Recombination 🎯 **NEET priority: Highest-yield.** *Part B of the single biggest chapter in NEET Biology (8–10 Q/year across both parts). **Genetic disorders** and **sex determination** alone are near-guaranteed marks β€” the exact karyotypes and inheritance patterns are asked verbatim.* ### Chromosomal Theory of Inheritance - Mendel published in **1865**, but his work went unrecognised until **1900** β€” for four reasons: poor communication of the era; his idea of discrete non-blending "factors" contradicted the observed continuous variation; his use of **mathematics** in biology was alien to contemporaries; and he had **no physical proof** of what factors were made of. - In **1900**, three scientists β€” **de Vries, Correns and von Tschermak** β€” independently rediscovered his results. Meanwhile improved microscopy revealed **chromosomes**, and by **1902** their meiotic movement was worked out. - **Walter Sutton and Theodore Boveri** noticed that chromosome behaviour exactly parallels gene behaviour β€” both occur in pairs, both segregate at gamete formation with only one of each pair going to a gamete, and both assort independently of other pairs. **Sutton** united chromosomal segregation with Mendelian principles into the **chromosomal theory of inheritance**. - **Thomas Hunt Morgan** experimentally verified it using ***Drosophila melanogaster*** β€” chosen because it grows on simple synthetic medium, completes its life cycle in about **two weeks**, gives a huge progeny from one mating, has clearly distinguishable sexes, and shows many hereditary variations visible under low magnification. ### Linkage & Recombination - Morgan crossed **yellow-bodied, white-eyed females Γ— brown-bodied, red-eyed males** and intercrossed the F1. The F2 ratio **deviated sharply from 9:3:3:1** β€” the two genes did NOT assort independently. - **Linkage** = the physical association of genes on the same chromosome, producing far more **parental** combinations than non-parental. **Recombination** = the generation of **non-parental** combinations. Both terms were coined by Morgan. - Linkage strength varies: **white and yellow** genes were **tightly linked** (only **1.3%** recombination), while **white and miniature wing** were **loosely linked** (**37.2%** recombination). **Alfred Sturtevant**, Morgan's student, used recombination frequency as a **measure of distance** between genes to build the first **genetic maps** β€” the same principle later used in the Human Genome Project. - **Trap:** higher recombination frequency means genes are **farther apart** and **more loosely linked**. Low recombination = tight linkage = genes close together. Students routinely invert this. ## Sex Determination β€” Four Systems ### Sex Determination β€” the four systems - **Henking (1891)** traced a nuclear structure through insect spermatogenesis and found **50% of sperm received it, 50% did not**. He named it the **X body** but couldn't explain its significance. Later work showed it was a chromosome β€” the **X chromosome**. Sex chromosomes were thus distinguished from **autosomes**. | **System** | **Female** | **Male** | **Which sex is heterogametic** | **Example** | | XO type | XX | XO (only one X, no Y) | Male | Grasshopper, many insects | | XY type | XX | XY | Male | Humans, Drosophila | | ZW type | ZW | ZZ | Female | Birds | | Haplodiploidy | Diploid (32 chromosomes) β€” queen/worker | Haploid (16 chromosomes) β€” drone | Neither (based on ploidy, not sex chromosomes) | Honey bee | ### Sex determination in humans - Humans have **23 pairs** of chromosomes: **22 pairs of autosomes** (identical in both sexes) + **1 pair of sex chromosomes**. Females are **XX**, males **XY**. - During spermatogenesis, **50% of sperm carry X** and **50% carry Y**; every ovum carries **only X**. So **the sperm determines the sex of the child**, and there is always a **50% probability** of either sex in each pregnancy β€” which is why blaming women for the sex of a child is scientifically false. ### Sex determination in honey bee β€” haplodiploidy - A **fertilised** egg β†’ **female** (queen or worker), diploid, **32 chromosomes**. An **unfertilised** egg β†’ **male (drone)** by **parthenogenesis**, haploid, **16 chromosomes**. - Three consequences NEET loves: drones produce sperm **by mitosis** (not meiosis β€” they're already haploid); they have **no father** and **cannot have sons**; but they **do have a grandfather** and **can have grandsons**. ## Mutation, Pedigree Analysis & Mendelian Disorders ### Mutation - **Mutation** alters DNA sequence, changing genotype and phenotype. Along with recombination, it is a major source of variation. - **Chromosomal aberrations** arise from **deletion** (loss) or **insertion/duplication** (gain) of a DNA segment β€” commonly observed in **cancer cells**. - **Point mutation** = change in a **single base pair**; the classic example is **sickle-cell anaemia**. Deletions and insertions of base pairs cause **frame-shift mutations**. - **Mutagens** are physical/chemical agents that induce mutation β€” e.g. **UV radiation**. ### Pedigree analysis - Since controlled crosses are impossible in humans, **pedigree analysis** β€” tracing a trait through a family tree across generations β€” is the alternative tool for determining whether a trait is dominant/recessive and autosomal/sex-linked. ### Mendelian disorders β€” caused by single-gene mutation | **Disorder** | **Inheritance** | **Defect** | **Key facts** | | Colour blindness | X-linked recessive | Defect in red or green cone of the eye | About 8% of males but only 0.4% of females affected β€” males have only one X | | Haemophilia | X-linked recessive | A single clotting-cascade protein is affected | A simple cut causes non-stop bleeding; carrier females transmit to sons; Queen Victoria's pedigree is the classic case | | Sickle-cell anaemia | Autosomal recessive | Glutamic acid β†’ Valine at the 6th position of the Ξ²-globin chain (codon GAG β†’ GUG) | Only HbΛ’HbΛ’ homozygotes are diseased; HbᴬHbΛ’ are unaffected carriers. RBC sickles under LOW oxygen tension | | Phenylketonuria | Autosomal recessive | Lacks the enzyme converting phenylalanine β†’ tyrosine | Phenylalanine accumulates as phenylpyruvic acid, causing mental retardation; excreted in urine | | Thalassemia | Autosomal recessive | Mutation/deletion reducing the RATE of globin chain synthesis | Ξ±-thalassemia: genes HBA1 + HBA2 on chromosome 16. Ξ²-thalassemia: gene HBB on chromosome 11 | **The distinction NEET tests:** thalassemia is a **QUANTITATIVE** problem β€” too few globin molecules made. Sickle-cell anaemia is a **QUALITATIVE** problem β€” a normal quantity of incorrectly-functioning globin. ## Chromosomal Disorders & Why This Matters for NEET ### Chromosomal disorders β€” caused by abnormal chromosome number/arrangement - **Aneuploidy** = gain or loss of chromosome(s), from **failure of chromatid segregation** during cell division. **Trisomy** = one extra copy; **monosomy** = one missing. - **Polyploidy** = gain of a whole extra chromosome SET, from **failure of cytokinesis** after telophase. Common in **plants**. | **Disorder** | **Karyotype** | **Cause** | **Features** | | Down's syndrome | Trisomy of chromosome 21 (47) | Extra copy of chromosome 21 | First described by Langdon Down (1866). Short stature, small round head, furrowed tongue, partially open mouth, broad palm with characteristic crease, retarded physical/psychomotor/mental development | | Klinefelter's syndrome | 47, XXY | Extra copy of X chromosome in a male | Overall masculine development BUT feminine features also expressed (gynaecomastia β€” breast development). Sterile | | Turner's syndrome | 45, XO | Absence of one X chromosome in a female | Sterile β€” ovaries are rudimentary; lacks other secondary sexual characters | ### Why this matters for NEET - High-value one-liners: chromosomal theory = **Sutton and Boveri**, verified by **Morgan** on **Drosophila**; genetic maps = **Sturtevant**; grasshopper = **XO**, birds = **ZW (female heterogametic)**, honey bee = **haplodiploid**; Down's = **trisomy 21**, Klinefelter = **47 XXY**, Turner = **45 XO**; sickle-cell = **Gluβ†’Val at position 6** of the Ξ²-chain. - **Trap:** Klinefelter (47, XXY) is a **male** with an extra X; Turner (45, XO) is a **female** missing an X β€” students swap these constantly. Also, **aneuploidy** comes from failed chromatid segregation while **polyploidy** comes from failed cytokinesis β€” different mechanisms entirely. And sickle-cell RBCs deform under **LOW** oxygen tension, not high. ## Test Yourself: MCQs, PYQs & Active Recall Answer these, then close the article and do an Active Recall. Reveal each answer only after you commit to one. ## Practice Questions **Q1.** The chromosomal theory of inheritance was proposed by: - (a) Mendel - (b) Sutton and Boveri - (c) Morgan and Sturtevant - (d) de Vries and Correns **Answer: (b)** β€” Walter Sutton and Theodore Boveri noted the parallel between chromosome and gene behaviour; Sutton formulated the chromosomal theory. **Q2.** Mendel's work was rediscovered in 1900 by: - (a) Sutton, Boveri and Morgan - (b) de Vries, Correns and von Tschermak - (c) Henking, Down and Turner - (d) Morgan, Sturtevant and Bridges **Answer: (b)** β€” de Vries, Correns and von Tschermak independently rediscovered Mendel's results in 1900. **Q3.** Thomas Hunt Morgan experimentally verified the chromosomal theory using: - (a) Pisum sativum - (b) Neurospora crassa - (c) Escherichia coli - (d) Drosophila melanogaster **Answer: (d)** β€” Morgan used the fruit fly Drosophila melanogaster β€” quick life cycle, large progeny, distinguishable sexes and many visible variations. **Q4.** In Morgan's experiments, a higher recombination frequency between two genes indicates that they are: - (a) Tightly linked and close together - (b) Loosely linked and farther apart - (c) Not inherited at all - (d) On different chromosomes **Answer: (b)** β€” Higher recombination frequency means the genes are farther apart and more loosely linked; low recombination means tight linkage. **Q5.** Genetic maps were first constructed using recombination frequency by: - (a) Thomas Hunt Morgan - (b) Henking - (c) Alfred Sturtevant - (d) Walter Sutton **Answer: (c)** β€” Sturtevant, Morgan's student, used recombination frequency between gene pairs as a measure of distance to map gene positions. **Q6.** The 'X body' observed during insect spermatogenesis was named by: - (a) Sutton - (b) Henking - (c) Morgan - (d) Boveri **Answer: (b)** β€” Henking (1891) traced the structure and named it the X body, though he could not explain its significance. **Q7.** In grasshoppers, the mechanism of sex determination is: - (a) Haplodiploid - (b) XY type - (c) XO type - (d) ZW type **Answer: (c)** β€” Grasshoppers show XO type β€” males have only one X besides the autosomes, females have a pair of X chromosomes. **Q8.** In birds, the heterogametic sex is: - (a) Neither β€” sex is determined by ploidy - (b) Both are homogametic - (c) Male (ZZ) - (d) Female (ZW) **Answer: (d)** β€” In birds, females are ZW (heterogametic) and males are ZZ (homogametic) β€” female heterogamety. **Q9.** A drone (male honey bee) has how many chromosomes? - (a) 46 - (b) 8 - (c) 16 - (d) 32 **Answer: (c)** β€” Drones develop from unfertilised eggs by parthenogenesis and are haploid with 16 chromosomes; females are diploid with 32. **Q10.** Male honey bees produce sperm by: - (a) They do not produce sperm - (b) Mitosis - (c) Binary fission - (d) Meiosis **Answer: (b)** β€” Since drones are already haploid, they produce sperm by mitosis rather than meiosis. **Q11.** A change in a single base pair of DNA is called: - (a) Chromosomal aberration - (b) Polyploidy - (c) Frame-shift mutation - (d) Point mutation **Answer: (d)** β€” A point mutation is a change in a single base pair; sickle-cell anaemia is the classic example. **Q12.** Colour blindness occurs in approximately what percentage of males? - (a) 50 per cent - (b) 0.4 per cent - (c) 8 per cent - (d) 25 per cent **Answer: (c)** β€” Red-green colour blindness affects about 8 per cent of males but only about 0.4 per cent of females. **Q13.** In sickle-cell anaemia, the amino acid substitution is: - (a) Glutamic acid replaced by valine at position 6 - (b) Lysine replaced by serine at position 10 - (c) Valine replaced by glutamic acid at position 6 - (d) Glycine replaced by alanine at position 4 **Answer: (a)** β€” Glutamic acid (Glu) is replaced by Valine (Val) at the sixth position of the beta globin chain, from codon GAG to GUG. **Q14.** Which genotype shows the diseased sickle-cell phenotype? - (a) HbA HbS - (b) All three genotypes - (c) HbS HbS - (d) HbA HbA **Answer: (c)** β€” Only homozygous HbS HbS individuals show the disease; heterozygous HbA HbS individuals are unaffected carriers. **Q15.** Aneuploidy results from: - (a) UV radiation only - (b) A single base substitution - (c) Failure of cytokinesis after telophase - (d) Failure of chromatid segregation during cell division **Answer: (d)** β€” Aneuploidy (gain or loss of a chromosome) results from failure of chromatid segregation; failed cytokinesis causes polyploidy. **Q16.** The karyotype of Klinefelter's syndrome is: - (a) 45, XO - (b) 47, XXY - (c) 47 with trisomy 21 - (d) 46, XY **Answer: (b)** β€” Klinefelter's syndrome is 47, XXY β€” an extra X chromosome in a male, producing gynaecomastia and sterility. **Q17.** The pedigree shown most likely represents a trait that is inherited as - (a) autosomal dominant - (b) X-linked recessive - (c) autosomal recessive - (d) X-linked dominant **Answer: (c)** β€” Two unaffected parents have an affected daughter, so the trait is recessive. Because the affected daughter has an unaffected father, it cannot be X-linked recessive (such a daughter would need an affected father). The trait is therefore autosomal recessive. **Q18.** Which statement about the pedigree is correct? - (a) The trait appears in every generation - (b) The affected female in generation II must be homozygous dominant - (c) Both parents in generation I must be heterozygous carriers - (d) The unaffected male in generation II must be a carrier **Answer: (c)** β€” The affected daughter in generation II is homozygous recessive, so each of her unaffected parents must carry one copy of the recessive allele β€” both are heterozygous. Her unaffected brother may be homozygous dominant or a carrier, and the trait skips generation II's other members and generation I, so it does not appear in every generation. ### NEET Previous Year Questions (PYQs) *Real NEET previous-year questions on this chapter, with explanations in our own words.* **Q19.** Turner's syndrome is characterised by the karyotype: (NEET PYQ) - (a) 47, +21 - (b) 45, XO - (c) 46, XX - (d) 47, XXY **Answer: (b)** β€” Turner's syndrome results from the absence of one X chromosome in a female β€” 45, XO. Such females are sterile with rudimentary ovaries. **Q20.** Down's syndrome is caused by: (NEET PYQ) - (a) An extra Y chromosome - (b) Trisomy of chromosome 21 - (c) Monosomy of chromosome 21 - (d) Loss of an X chromosome **Answer: (b)** β€” Down's syndrome is caused by an additional copy of chromosome 21 (trisomy 21), first described by Langdon Down in 1866. **Q21.** Thalassemia differs from sickle-cell anaemia in that thalassemia is: (NEET PYQ) - (a) A qualitative problem of incorrectly functioning globin - (b) Not inherited - (c) A quantitative problem of synthesising too few globin molecules - (d) Caused by a chromosomal aberration **Answer: (c)** β€” Thalassemia is a quantitative defect (too few globin chains made); sickle-cell anaemia is a qualitative defect (incorrectly functioning globin). **Q22.** Haemophilia is transmitted: (NEET PYQ) - (a) From an unaffected carrier female to some male progeny - (b) From affected father to all daughters equally - (c) Only to female offspring - (d) Only through autosomes **Answer: (a)** β€” Haemophilia is an X-linked recessive disease shown transmitting from an unaffected carrier female to some of her male progeny. **Q23.** In beta-thalassemia, the affected gene HBB is located on chromosome: (NEET PYQ) - (a) Chromosome 16 - (b) Chromosome 11 - (c) Chromosome 21 - (d) The X chromosome **Answer: (b)** β€” Beta-thalassemia is controlled by the single gene HBB on chromosome 11; alpha-thalassemia involves HBA1 and HBA2 on chromosome 16. **Q24.** Phenylketonuria results from the lack of an enzyme that converts: (NEET PYQ) - (a) Glucose to glycogen - (b) Tyrosine to phenylalanine - (c) Phenylalanine to tyrosine - (d) Glutamic acid to valine **Answer: (c)** β€” Affected individuals lack the enzyme converting phenylalanine to tyrosine, so phenylalanine accumulates as phenylpyruvic acid. **Q25.** The genes for white eye and yellow body in Drosophila showed a recombination frequency of: (NEET PYQ) - (a) 1.3 per cent - (b) 50 per cent - (c) 0 per cent - (d) 37.2 per cent **Answer: (a)** β€” White and yellow were very tightly linked, showing only 1.3 per cent recombination; white and miniature wing showed 37.2 per cent. **Q26.** Polyploidy, an increase in whole sets of chromosomes, results from: (NEET PYQ) - (a) Failure of cytokinesis after telophase - (b) Failure of chromatid segregation - (c) Crossing over - (d) Point mutation **Answer: (a)** β€” Failure of cytokinesis after the telophase stage increases whole chromosome sets β€” polyploidy, often seen in plants. ### Active Recall Prompt Write everything you can recall about **Principles of Inheritance and Variation (Part B)**, naming each part first: the **chromosomal theory of inheritance** (why Mendel was ignored, the 1900 rediscovery, Sutton and Boveri, Morgan and Drosophila); **linkage and recombination** (what Morgan found, tight vs loose linkage, Sturtevant's maps); **sex determination** (XO, XY, ZW and haplodiploid systems, with examples, plus humans and honey bees); **mutation** (chromosomal aberration, point mutation, frame-shift, mutagens); **pedigree analysis**; **Mendelian disorders** (colour blindness, haemophilia, sickle-cell anaemia, phenylketonuria, thalassemia β€” inheritance pattern and defect for each); and **chromosomal disorders** (aneuploidy vs polyploidy; Down's, Klinefelter's and Turner's syndromes with their karyotypes). Begin each fact with its topic and end it with a full stop.