This presentation deals with the basics of Genetics, a little about the Human Genome Project and just a touch on Genodermatosis & Chromosomal Disorders

1. GENETICS IN DERMATOLOGY

2. GENETICS (Gk: Genesis – Origin)
The branch of biology that deals with heredity,
especially the mechanisms of hereditary
transmission and the variation of inherited
characteristics among similar or related
organisms

4. HUMAN GENOME ORG

6. GENETICS : PRINCIPLES
• GENE (Grk ‘Genea’ – Descent)
Basic Unit of Heredity
Info to Build / Maintain Cells
& Transfer traits to Offspring
Sequence of DNA bases

7. GENETICS : PRINCIPLES
• CHROMOSOME
Storage Units of Genes
Females
23 Homologous Pairs
22 AUTO + 01 ALLO
each Somatic Cell
22 Homologous + 01 Heterologous pair - Males

8. GENE LOCUS
Genes arranged in
specific location on
Chromosome - LOCI

9. GENETICS : PRINCIPLES
ALLELE - Alternative genes at
Single Locus
HETEROZYGOUS (Aa)
HOMOZYGOUS (AA)

10. GENETICS : PRINCIPLES
GENOTYPE - Inherited Instructions within an
Organism’s genetic code;
Blueprint, Constant, Str / Func
PHENOTYPE - Observable traits like
Morphology, Properties, Changes
with Environmental Influence &
Developmental Conditions

11. PENETRANCE
Proportion of individuals who carry a disease
causing mutated gene and exhibit the clinical
phenotype over a defined period.
Failure to exhibit Phenotype even though they
carry the affected gene; this condition is termed
as REDUCED / INCOMPLETE PENETRANCE
AD Dis e.g. TUBEROUS SCLEROSIS

12. GENETICS : PRINCIPLES
DOMINANT ALLELES - Phenotypic Expression
with Heterozygous Allele
RECESSIVE ALLELES - Phenotypic Expression
only with Homozygous Alleles

13. GENETIC HETEROGENICITY
• EXACT CLINICAL PHENOTYPES due to several
Gene Mutations
• LAMELLAR ICHTHYOSIS
Mut in TGM-1 / ABCA12 / CYP4F22

14. CLINICAL HETEROGENICITY
• Mut in Single-Gene-Locus  Several
Phenotypic Variants
E.g. Mut in Connexin 26 causing
Vohwinkel Syn
Keratitis-ichthyosis-deafness (KID) Syn

15. MOSAICISM
Presence in an individual of 2 (or more)
genetically distinct cell populations derived from
the same homozygous zygote.
Functional Mosaicism - Normal Human Female
with 46, XX (One X Chr inactivated during
Embryogenesis by Lyonization into Barr Body)

16. MITOSIS
Cellular Growth / Repair / Asexual Reproduction
1 Parent Cell  2 Diploid Cells (2n)
Identical Daughter Cells

17. MEIOSIS
Sexual Reproduction / Production of Gametes
1 Parent Cell  4 Haploid Cells (n)
Daughter Cells different from Parent Cells
Chromosomal Cross-Over

18. CELL DIVISION

19. NOSOLOGY (Gk ; Nosos + Logos)
•FAMILIAL - ‘Clustering’ Higher Prevalence
in relatives than population
eg HAILEY-HAILEY DIS
•CONGENITAL - present since Birth +/- Genetic
-Developmental Defects-
Infectious (RUBELLA)
Insult (AMNIOTIC BAND SYN)

20. NOSOLOGY

21. POLYGENIC
Multifactorial
Multiple Genes + Environmental Influences
ATOPIC DERMATITIS
PSORIASIS VULGARIS

22. GENODERMATOSES
• INHERITED DISORDERS
Alteration in Function of SINGLE GENE
Typical Inheritance Patterns
AD / AR / XD / XR

23. AUTOSOMAL DOMINANT
Both Sexes
Heterozygous
For Abn Allele
‘AFFECTED’
50% Transmission
(Average)
Positive Family History

24. AUTOSOMAL DOMINANT
Acute intermittent porphyria PBG
Ichthyosis (some forms) FILAGGRIN
Neurofibromatosis NF1
Tuberous sclerosis TSC1/2
Hereditary haemorrhagic telangiectasia ENG

25. AUTOSOMAL RECESSIVE
Both Sexes
Homogenous for
Abn Allele is
‘AFFECTED’
25% Transmission
No Family History (Carriers)

26. AR
Consanguinous Marriages / Ethnic Groups
(Isolated Allele Groups)

Increased Risk of Carrier Parents

Risk of Affected Individual (25%)

27. AUTOSOMAL RECESSIVE (AR)
Epidermolysis bullosa DSP
Severe Ichthyosis ABCA12
Acrodermatitis enteropathica SLC39A4
Phenylketonuria PAH
Xeroderma pigmentosum XPA/B/C/D

28. X-LINKED DOMINANT
Hemizygous Male
Heterozygous Female
Affected Male
to Daughters
Affected Female
To 50% each
Son/Daughter

29. X-LINKED DOMINANT (XD)
Incontinentia pigmenti NEMO
Oro-facial-digital syndrome OFD1

30. X-LINKED RECESSIVE
Usually Males
Atavistic
No Father to Son
Carrier Mother : SON
One Daughter Carrier

31. X-LINKED RECESSIVE (XR)
Anhidrotic ectodermal dysplasia EDA
Fabry’s disease A-GAL A
Menke’s syndrome ATP7A
Ocular albinism GPR143

32. CHROMOSOMAL DISORDERS
DEFECTS :
Change in no of Chr (ANEUPLOIDY)
Monosomy - TURNER’S SYN
Trisomy - DOWN’S
EDWARD’S
PATAU’S

33. CHROMOSOMAL DISORDERS
DEFECTS :
Chr Str Rearrangement
Deletion - CRI-DU-CHAT
Translocation - BURKITT’S LYMPHOMA
Non-Dysjunction - KLEINFELTER’S
DOWN’S

34. CHROMOSOMAL DISORDERS
• DEFECTS
based on Chromosomes involved
AUTOSOMES SEX CHROMOSOMES
DOWN’S / EDWARD’S TURNER’S / KLEINFELTERS
PATAU’S / CRI-DU-CHAT FRAGILE-X / XXY / XXYY /
CHR 4p DEL / CHR 18q DEL XXXXY

35. DOWN’S SYN
47, XX(XY), +21 1:700 LB ‘MONGOLIAN SYN’

36. DS – SYSTEMIC MANIFEST

37. DS – DERMAT MANIFEST
Birth - Soft, Velvety Skin
5 and 10 YO - Dry / Less Elastic
15 YO – Generalized Xerosis
20 YO - Patchy Lichenidication
Folliculitis Assoc with Malassezia Furfur;
Responsive to Itraconazle
Assoc with

38. DS – DERMAT MANIFEST
Fine, Hypopigmented Hair
Assoc with Alopecia Arreata
Recurrent Skin infections, Angular Cheilitis
Assoc with Onychomycosis

39. OTHER AUTOSOMAL DIS
EDWARD’S SYN 47,XX(XY),+18
Hypomelanosis
CRI-DU-CHAT SYN 46,XX(XY),-5p
Premature Greying of Hair
LONG-ARM-DELETION-18 46,XX(XY),-18q
Eczema (25%)

40. TURNER’S SYN
45,XO 1:2500 LBs

41. TURNER’S SYN-MANIFEST

42. TURNER’S SYN-DERMAT FEATURES
• Hypoplastic Nails
• Keloidal Tendency
• Melanocytic Naevi  Melanoma

43. KLEINFELTER’S SYNDROME
• 47,XXY 1:600 LBs
• Assoc with SLE
INCONTINENTIA PIGMENTI
LIVEDOID VASCULITIS
LEG ULCERS

44. THANK YOU